Asclepias Fruticosa

Context: Ficus racemosa Linn. (Moraceae) bark is a rich source of phenolic compounds having diverse biological properties including antioxidant activity. The present study evaluated the cardioprotective activity of sequential acetone extract of Ficus racemosa bark against doxorubicin-induced cardiotoxicity in rats.

Materials and methods: The extract was standardized by high-performance liquid chromatography (HPLC) and subjected to acute toxicological evaluation in mice. Cardiotoxicity was induced by administration of doxorubicin (10?mg kg^?1 i.v.) to the extract pretreated rats (250 and 500?mg kg^?1) and compared with that of Arjuna, a standard cardiotonic. Biochemical parameters included CK-MB, LDH, AST, ALT, troponin I, thiobarbituric acid reactive substances (TBARS), and glutathione.

Results: The HPLC fingerprinting of the extract indicated the presence of bergenin (0.89%) and bergapten (0.07%). In an acute toxicity study, the extract at a dose of 2?g kg^?1 did not cause any adverse changes and no mortality was observed. Administration of doxorubicin significantly increased (p?≤?0.05) serum levels of creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase, which were decreased to an extent of 68, 63, 41, and 65%, respectively, in extract pretreated group (500?mg kg^?1). Troponin I was undetected in control group, while it was found in serum of all the experimental groups. The extract pretreatment significantly decreased (p?≤?0.05) TBARS and increased glutathione levels in serum and cardiac tissue. These observations were further substantiated by the histopathological studies.

Conclusion: The acetone extract of F. racemosa bark possesses potential cardioprotective activity against doxorubicin-induced cardiotoxicity in rats by scavenging free radicals generated by the administration of the drug.     

Protective effects of berberine against doxorubicin-induced cardiotoxicity in rats by inhibiting metabolism of doxorubicin

Abstract

1.?The clinical use of doxorubicin, an effective anticancer drug, is severely hampered by its cardiotoxicity. Berberine, a botanical alkaloid, has been reported to possess cardioprotective and antitumor effects. In this study, we investigated the cardioprotective effect of berberine on doxorubicin-induced cardiotoxicity and the effect of berberine on the metabolism of doxorubicin.

2.?Adult male Sprague-Dawley rats were administered doxorubicin in the presence or absence of berberine for 2 weeks. Administration of berberine effectively prevented doxorubicin-induced body weight reduction and mortality in rats.

3.?Berberine reduced the activity of myocardial enzymes, including aspartate aminotransferase (AST), creatine kinase (CK), CK isoenzyme (CK-MB) and lactate dehydrogenase (LDH). Echocardiographic examination further demonstrated that berberine effectively ameliorated cardiac dysfunction induced by doxorubicin.

4.?Berberine inhibited the metabolism of doxorubicin in the cytoplasm of rat heart and reduced the accumulation of doxorubicinol (a secondary alcohol metabolite of doxorubicin) in heart.

5.?These data showed that berberine alleviated the doxorubicin-induced cardiotoxicity in rats via inhibition of the metabolism of doxorubicin and reduced accumulation of doxorubicinol selectively in hearts.     

Cardioprotective effect of whole fruit extract of pomegranate on doxorubicin-induced toxicity in rat

Context: Cardioprotective effects of various plants are generally attributed to their antioxidant activity. The whole fruit extract of pomegranate (WFEP), Punica granatum L. (Punicaceae), has a potent antioxidant activity.

Objective: To investigate cardioprotective effect of WFEP against doxorubicin (Dox)-induced cardiotoxicity in rats.

Materials and methods: Male Wistar rats were divided randomly into three groups of eight rats each: control (water, 5?mL/kg); Dox (10?mg/kg i.v.) and WFEP (100?mg/kg). Dox was administered in Dox and WFEP groups. After anesthetizing the animals on the last day, electrocardiogram was recorded and blood was analyzed for creatine kinase-MB isoenzyme (CK-MB), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) activities. Determinations of superoxide dismutase (SOD), reduced glutathione (GSH), lipid peroxidation (LPO) and histopathology of the heart tissues were carried out.

Results: The WFEP group showed decreased QT and increase in heart rate (p?<?0.05) compared to the Dox group. Significant decrease in CK-MB (p?<?0.01), LDH (p?<?0.05) and no such significant decrease in AST were observed as compared to the Dox group. There was significant increase in the level of GSH (p?<?0.05), whereas inhibition of LPO and increase in SOD concentration was not significant in the WFEP group compared to the Dox group. Histopathological study of the WFEP-treated group showed slight protection against myocardial toxicity induced by Dox.

Conclusion: Results indicate that WFEP has cardioprotective effect against Dox-induced cardiotoxicity in rats.     

Phoenix dactylifera seeds ameliorate early diabetic complications in streptozotocin-induced diabetic rats

Abstract

Context: In Arabic folk medicine, the seeds of Phoenix dactylifera L. (Arecaceae) have been used to manage diabetes for many years. Few studies have reported the antidiabetic effect of P. dactylifera seeds; however, their effect on diabetic complications is still unexplored.

Objective: The present study investigates the protective effect of P. dactylifera seeds against diabetic complications in rats.

Material and methods: The aqueous suspension of P. dactylifera seeds (aqPDS) (1?g/kg/d) was orally administered to streptozotocin-induced diabetic rats for 4 weeks. The serum biochemical parameters were assessed spectrophotometrically. Furthermore, oxidative stress was examined in both liver and kidney tissues by assessment of thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), reduced glutathione, superoxide dismutase (SOD), glutathione S-transferase, and catalase.

Results: Oral administration of aqPDS significantly ameliorated the elevated levels of glucose (248?±?42 versus 508?±?60?mg/dl), urea (32?±?3.3 versus 48.3?±?5.6?mg/dl), creatinine (2.2?±?0.35 versus 3.8?±?0.37?mg/dl), ALT (29.6?±?3.9 versus 46.4?±?5.9?IU/l), and AST (73.3?±?13 versus 127.8?±?18.7?IU/l) compared with the untreated diabetic rats. In addition to significant augmentation in the activities of antioxidant enzymes, there was reduction in TBARS and NO levels and improvement of histopathological architecture of the liver and kidney of diabetic rats.

Discussion and conclusion: The aqPDS showed potential protective effects against early diabetic complications of both liver and kidney. This effect may be explained by the antioxidant and free radical scavenging capabilities of P. dactylifera seeds.     

Effects of folic acid and vitamin B complex on serum C-reactive protein and albumin levels in stable hemodialysis patients

ABSTRACT

Objective: Folic acid and vitamin B complex administration in uremic patients has been reported to lower plasma total homocysteine (tHcy) levels, but whether or not this has a beneficial effect on the inflammatory state is not clear.

Methods: We conducted a randomized open labeled study to determine the effects of folic acid (5?mg daily) and vitamin B complex administration on plasma tHcy levels as well as inflammatory (serum high-sensitivity C reactive protein, hs?CRP) and nutritional (serum albumin) markers in patients on maintenance hemodialysis. Treatment was given for 3 consecutive months to 61 patients on maintenance hemodialysis. Another 60 patients, all age-, sex-, hemodialysis duration-matched served as control group.

Main outcome measures: Plasma tHcy, serum hs?CRP, albumin, creatinine (Cr), post-dialysis body weight (BW), and normalized protein catabolism rate (nPCR).

Results: After 3 months, levels of plasma tHcy and serum hs?CRP, Cr, and nPCR were significantly decreased while levels of serum albumin, vitamin B₁₂, folate, and BW were significantly increased. The dialytic dose (KT/V) and dietary intake remained unchanged. However, correlations between the magnitude of reduction of tHcy & hs?CRP, tHcy & Cr, and Cr & nPCR were statistically significant.

Conclusions: Folic acid and vitamin B complex co-administration effectively lowers tHcy and hs?CRP levels and increases albumin levels in stable hemodialysis subjects, underscoring their potential benefit to attenuate the state of inflammation and possibly improve the nutritional status in patients on hemodialysis.     

Essential oil of Psidium cattleianum leaves: Antioxidant and antifungal activity

Abstract

Context: Psidium cattleianum Sabine (Myrtacea) is rich in vitamin C and phenolic compounds, including epicatechin and gallic acid as the main components.

Objective: To evaluate the antifungal and antioxidant capacity in vitro of the essential oil of araçá (EOA). The acute toxicity of the EOA also was evaluated in mice.

Materials and methods: The leaves of the P. cattleianum were extracted by steam distillation. The antioxidant capacity was evaluated by in vitro tests [1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS), ferric ion reducing antioxidant power (FRAP), linoleic acid oxidation, thiobarbituric acid reactive species (TBARS)], and ex vivo analysis [TBARS, δ-aminulevunilate dehydratase (δ-Ala-D) and catalase activity, non-protein thiols (NPSH), and ascorbic acid levels]. The toxicity was studied in mice by a single oral administration of EOA; and the antifungal activity was performed with five strains of fungi.

Results: The EOA exhibited antioxidant activity in the FRAP assay and reduced lipid peroxidation in the cortex (I_max?=?32.90?±?2.62%), hippocampus (IC₅₀?=?48.00?±?3.00?µg/ml and I_max?=?32.90?±?2.62%), and cerebellum (I_max?=?45.40?±?14.04%) of mice. Acute administration of the EOA by the oral route did not cause toxicological effects in mice (LD₅₀?>?500?µg/ml). The EOA also showed antifungal activity through of the determination minimum inhibitory concentration (MIC) values ranging from 41.67?±?18.04 to 166.70?±?72.17?µg/ml for tested strains.

Conclusion: The results of present study indicate that EOA possess antioxidant properties, antifungal and not cause toxicity at tested doses.     

Cardioprotective effects of rosuvastatin and carvedilol on delayed cardiotoxicity of doxorubicin in rats

Context: Doxorubicin is widely used anti-neoplastic drug but has serious cardiotoxicity. Long-term cardioprotective effects of statin and carvedilol against delayed cardiotoxicity of doxorubicin was not well elucidated.

Objective: To evaluate long-term cardioprotective effects of co-administered rosuvastatin and carvedilol against chronic doxorubicin-induced cardiomyopathy (DIC) in rats.

Methods: Sixty-one rats were assigned to six groups: group I, control; group II, doxorubicin only (1.25 mg/kg, bi-daily, I.P.); group III, doxorubicin + rosuvastatin (2 mg/kg/day, P.O.); group IV, doxorubicin + rosuvastatin(10 mg/kg/day, P.O.); group V, doxorubicin + carvedilol (5 mg/kg/day, P.O.); group VI, doxorubicin + carvedilol (10 mg/kg/day, P.O.). Drugs were administered for 4 weeks (by week 4) and rats were observed without drugs for 4 weeks (by week 8).

Results: After 4 weeks discontinuation of drugs (week 8), group III showed higher +dP/dt (p = 0.058), lower ?dP/dt (p = 0.009), lower left ventricular (LV) tissue malondialdehyde (MDA; p = 0.022), and less LV fibrosis (p = 0.011) than group II. Group IV showed similar results to group III. However, in group V and VI, carvedilol failed to reduce LV dysfunction, elevation of troponin or myocardial fibrosis, although group V showed lower LV tissue MDA (p = 0.004) than group II.

Discussion and conclusions: Myocardial injury and LV systolic/diastolic dysfunction at week 8 was alleviated by co-administered rosuvastatin, but not by carvedilol. It is unclear whether the cardioprotective effect of rosuvastatin is attributed to a suppression of oxidative stress induced by doxorubicin, because carvedilol did not exhibit a cardioprotective effect despite its antioxidant effects.     

Cardioprotective effect of grape-seed proanthocyanidins on doxorubicin-induced cardiac toxicity in rats

Context: Doxorubicin (Dox) is an anthracycline antibiotic used as anticancer agent. However, its use is limited due to its cardiotoxicity which is mainly attributed to accumulation of reactive oxygen species.

Objective: This study was conducted to assess whether the antioxidant, proanthocyanidins (Pro) can ameliorate Dox-induced cardiotoxicity in rats.

Materials and methods: Male Sprague–Dawely rats were divided into four groups. Group I was control. Group II received Pro (70?mg/kg, orally) once daily for 10 days. Group III received doxorubicin 15?mg/kg i.p. as a single dose on the 7th day and Group IV animals were treated with Pro once daily for 10 days and Dox on the 7th day. The parameters of study were serum biomarkers, cardiac tissue antioxidant status, ECG, and effect on aconitine-induced cardiotoxicity.

Results: Cardiac toxicity of doxorubicin was manifested as a significant increase in heart rate, elevation of the ST segment, prolongation of the QT interval and an increase in T wave amplitude. In addition, Dox enhanced aconitine-induced cardiotoxicity by a significant decrease in the aconitine dose producing ventricular tachycardia (VT). Administration of Pro significantly suppressed Dox-induced ECG changes and normalized the aconitine dose producing VT. The toxicity of Dox was also confirmed biochemically by significant elevation of serum CK-MB and LDH activities as well as myocardial MDA and GSH contents and decrease in serum catalase and myocardial SOD activities. Administration of Pro significantly suppressed these biochemical changes.

Discussion and conclusion: These results suggest that proanthocyanidins might be a potential cardioprotective agent against Dox-induced cardiotoxicity due to its antioxidant properties.     

Pooled analysis of GI tolerability of 21 randomized controlled trials of celecoxib and nonselective NSAIDs

ABSTRACT

Objective: To compare the gastrointestinal (GI) tolerability of celecoxib and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) at approved doses in patients with common musculoskeletal conditions.

Research design and methods: This was a retrospective, pooled analysis of studies selected from the Pfizer Corporate Clinical Trials Registry. Study selection criteria were: (1) Data available as of October 31, 2004; (2) Randomized, parallel-group study design and planned treatment duration of ≥?2 weeks; (3) At least one nonselective NSAID (naproxen, ibuprofen, or diclofenac) as a comparator; (4) At least one arm with 200?mg or 400?mg celecoxib per day; (5) Patients with osteoarthritis (OA), adult rheumatoid arthritis (RA), or ankylosing spondylitis (AS).

Data were pooled by treatment and by subject from the safety analysis population of each included study. Joint primary end points were the combined incidence of tolerability-related GI adverse events (AEs) (abdominal pain, dyspepsia, nausea, diarrhea, and flatulence), and time to study discontinuation due to any GI?AE.

Results: In all, 21 studies met the selection criteria. Across the safety analysis populations of the included studies, 7797 patients received celecoxib total daily dose 200?mg/day, 6653 received celecoxib total daily dose 400?mg/day, 2953 received naproxen, 499 received ibuprofen, and 5643 received diclofenac. Tolerability-related GI AEs were reported by significantly fewer celecoxib-treated patients (16.0%) than by those treated with naproxen (24.3%), ibuprofen (24.2%), or diclofenac (19.9%) (p?<?0.0001 vs. each comparator). Time to study discontinuation due to any GI?AE was significantly longer for celecoxib than for naproxen (p?<?0.0001), ibuprofen (p?=?0.002), or diclofenac (p?=?0.048). In the RA subpopulation (n?=?2857), there was no significant difference between the celecoxib and naproxen or ibuprofen groups in incidence of tolerability-related GI AEs and GI AEs.

Limitations: The limitations are inherent to the retrospective analysis design.

Conclusions: In this pooled analysis of celecoxib at approved doses in OA, RA, and AS, fewer celecoxib-treated patients in the overall population had tolerability-related GI AEs than patients treated with naproxen, ibuprofen, or diclofenac. In addition, celecoxib-treated patients had a significantly longer time to study discontinuation due to GI AEs.     

Protective effect of saffron extract against doxorubicin cardiotoxicity in isolated rabbit heart

Abstract

Context: Anticancer treatments such as anthracyclines are effective; however, they induce cardiotoxicity by releasing radical oxygen species (ROS). Saffron (Crocus sativus; Iridaceae) is a widely used spice with antioxidant properties and numerous health benefits that may provide cardioprotection.

Objective: To assess the effect of saffron against acute myocardium damage by anthracyclines compared with electrolysis as a free radical generating system.

Materials and methods: According to the Langendorff method, we used the model of an isolated rabbit heart perfused in retrograde. In one set of experiments, ROS was generated by electrolysis of the perfused heart solution (3?mA for 30?min) in the presence and absence of saffron extracts at the optimal dose (10?μg/ml). In another set, we perfused the heart with anthracycline, i.e. 30?μM doxorubicin (Doxo) in the presence and absence of 10?μg/ml saffron extracts. We evaluated cardiodynamics, as well as biochemical and pathological parameters, to emphasize the effectiveness of the treatment with saffron extract using the optimal dose of catalase (150?IU) as a positive control.

Results: ROS generated, respectively, by electrolysis and by Doxo significantly (p?<?0.05) affects cardiovascular function; it decreased ventricular pressure (45.02 and 40.41%), heart rate (36.31 and 22.39%) and coronary flow (50.98 and 36.67%). Increased lipid peroxidation of the myocardium was also observed (118.22 and 56.58%), while superoxide dismutase activity decreased (48.33 and 38.70%). The myocardial architecture was altered and the intercellular spaces increased.

Conclusion: Saffron perfused during electrolysis helps trap ROS and significantly improves myocardial function; however, saffron was less effective against Doxo, thus suggesting that mechanisms other than oxidative stress underlie Doxo cardiotoxicity.     

Evaluation of the JT and corrected JT intervals as a new ECG method for monitoring doxorubicin cardiotoxicity in the dog

A comparison was made of the sensitivity of ECG, ultrastructural heart pathology, and plasma enzymes CK-MB and α-HBDH as methods to assess doxorubicin cardiotoxicity in adult beagle dogs given doxorubicin 30 mg/m² i.v. once a week for three times. A progressive increase in JT and QT intervals, in corrected JT (JTc) and QT (QTc) intervals as well as a reduction in both T wave amplitude and RR duration, were observed in doxorubicin-treated dogs; the electrocardiogram (ECG) abnormalities were associated with doxorubicin-induced ultrastructural changes in cardiac tissue, consisting of dilation of the sarcoplasmic reticulum, multiform, flasklike invaginations of T-tubules containing electrondense material, and interruption of the junctional sarcoplasmic reticulum, which became more severe as the observation period progressed. On the contrary, doxorubicin treatment was associated with transient changes in plasma CK-MB and α-HBDH, which were unrelated to the severity of chronic cardiotoxicity. Overall results suggest that the monitoring of the ECG parameters related to the repolarization of the cardiac muscle, and particularly JT and JTc, might be regarded as a noninvasive method for the study of doxorubicin cardiotoxicity in the dog.     

Biocompatibility,absorption and safety of protein nanoparticle-based delivery of doxorubicin through oral administration in rats

Abstract

Doxorubicin, a potent anticancer drug associated with cardiotoxicity and low oral bioavailability, was loaded into apotransferrin nanoparticles to improve its pharmacological performance. Here, doxorubicin (doxo)-loaded apotransferrin nanoparticles were termed as Apodoxonano, and they were prepared by sol-oil chemistry. The pH-dependent stability of nanoparticles in simulated fluids was evaluated, and the in vitro release was investigated in phosphate-buffered saline. The pharmacokinetic and toxicity studies were conducted in Wistar rats. Nanoparticles have an average size of 75?nm, with 63% entrapment efficiency, at 10?mg w/w of apotransferrin. The particles displayed good pH-dependent stability in the pH range 1.1–7.4, but sensitive at endosomal pH of 5.5, thus facilitating intracellular drug release in endosomes. Multiplex assay showed high transport ability of nano form across epithelial cells (caco-2) when compared to doxo. Moreover, during oral administration, Apodoxonano localizes significantly in esophagus, stomach and small intestine, suggesting that it was absorbed in GI tract through epithelial lining. The drug localization was shown to be significantly lower in the heart reflecting its decreased cardiotoxic nature. The Apodoxonano with a longer bioavailability and a negligible cardiotoxicity can serve as an effective and safe vehicle of drug delivery.     

Overexpressed SIRT6 ameliorates doxorubicin-induced cardiotoxicity and potentiates the therapeutic efficacy through metabolic remodeling

Since the utilization of anthracyclines in cancer therapy, severe cardiotoxicity has become a major obstacle. The major challenge in treating cancer patients with anthracyclines is minimizing cardiotoxicity without compromising antitumor efficacy. Herein, histone deacetylase SIRT6 expression was reduced in plasma of patients treated with anthracyclines-based chemotherapy regimens. Furthermore,overexpression of SIRT6 alleviated doxorubicin-induced cytotoxicity in cardiomyocytes, and potentiated c...     

A short-time model to study relevant indices of cardiotoxicity of doxorubicin in the rat

Abstract

Aim: Short-time models (STM) to study the cardiotoxicity (acute or chronic) of doxorubicin in rats are of interest to assess protective interventions and pathways. STM promotes more ethical animal treatment with less stress, and at a lower cost compared to established long-time models (LTM). We wanted to investigate if an STM of 9?d yields the same information regarding cardiotoxicity as an LTM of 9 weeks.

Methods: Male Wistar rats received identical drug administration protocols in STM and LTM. The two intervention groups (n?=?6) received intraperitoneal (i.p.) injections of 2?mg/kg doxorubicin every day for five consecutive days, with a total cumulative dose of 10?mg/kg. The two control groups (n?=?6), received an equivalent volume of saline injected every day for five consecutive days. Hearts from STM and LTM were excised and Langendorff-perfused after 9?d or 9 weeks, respectively, after the first drug injection. Cardiotoxicity was assessed in paced Langendorff hearts by a release of hydrogenperoxide (H₂O₂) and troponin T (TnT) in effluent, by myocardial accumulation of doxorubicin and its metabolite doxorubicinol, and by physiological parameters recorded during pressure, or volume-regulated perfusion.

Results: In STM, hearts exposed to doxorubicin demonstrated a 15% reduction in left ventricular developed pressure (LVDP) irrespective of flow mode, and a 13% increase in aortic pressure (AoP), during volume-regulated perfusion, an index of coronary resistance, compared to controls. Left ventricular end-diastolic pressure (LVEDP) was increased by 72% during pressure-regulated perfusion and 100% during volume-regulated perfusion in STM. In LTM, hearts exposed to doxorubicin demonstrated a 40% reduction in LVDP during pressure-regulated perfusion and a 20% reduction during volume-regulated perfusion. LVEDP was 70% higher in doxorubicin-treated hearts during pressure-regulated perfusion and 80% higher during volume-regulated perfusion. In addition, aortic pressure was increased by 30% during volume-regulated perfusion. In both STM and LTM, hearts exposed to doxorubicin demonstrated a higher H₂O₂ and TnT release, compared to respective controls. The difference was most pronounced in STM. Myocardial content of doxorubicin was detectable in both STM and LTM. However, doxorubicinol was only detectable in STM.

Conclusion: STM is comparable to LTM to study relevant indices of cardiotoxicity of doxorubicin in rat hearts. Biochemical differences are more pronounced in STM, while contractile differences are more pronounced in LTM. STM could be a preferred model for preliminary studies of protective interventions.     

Chronic effects of a novel synthetic anthracycline derivative (SM-5887) on normal heart and doxorubicin-induced cardiomyopathy in beagle dogs

This study was designed to investigate the chronic cardiotoxic potential of SM-5887 and a possible deteriorating effect of SM-5887 on low-grade cardiotoxicity pre-induced by doxorubicin in beagle dogs. In the chronic treatment, beagle dogs of each sex were given intravenously once every 3 weeks, either a sublethal dose of doxorubicin (1.5 mg/kg) or SM-5887 (2.5 mg/kg). The experiment was terminated 3 weeks after the ninth dosing. Animals which received over six courses of doxorubicin demonstrated the electrocardiogram (ECG) changes, decrease of blood pressure and high-grade histopathological cardiomyopathy, while animals which were terminally sacrificed after the SM-5887 administration did not show any changes in ECG, blood pressure and histopathological examinations. To examine a possibly deteriorating cardiotoxic effect of SM-5887, low-grade cardiomyopathy was induced in dogs by four courses of doxorubicin (1.5 mg/kg). Nine weeks after pre-treatment, dogs were given four courses of either doxorubicin (1.5 mg/kg) or SM-5887 (2.5 mg/kg) once every 3 weeks. The low-grade cardiotoxic changes were enhanced by the additional doxorubicin treatment. On the contrary, the SM-5887 treatment did not progress the grade of cardiomyopathy. In conclusion, SM-5887 does not have any potential of chronic cardiotoxicity and deteriorating effect on doxorubicin-induced cardiotoxicity in dogs.     

Memory restorative ability of clioquinol in copper–cholesterol-induced experimental dementia in mice

Abstract

Context: Results from various studies indicate that the presence of certain heavy metals such as aluminum (Al), arsenic (As), copper (Cu), lead (Pb), and mercury (Hg) may enhance the aggregation of Aβ and oxidative stress levels leading to neuronal toxicity and Alzheimer’s disease (AD). Studies also reveal that anomalous brain copper–cholesterol (Cu–Ch) homeostasis may lead to memory deficits in Swiss albino mice.

Objective: The present study investigates the anti-amnesic potential of clioquinol (5-chloro-7-iodoquinolin-8-ol) in cognitive deficits associated with experimental dementia induced by Cu–Ch.

Materials and methods: Administration of Cu–Ch {0.21?mg/kg, per os – 2% w/v, per os for 8 weeks} was used to induce dementia in Swiss albino mice. The Morris water maze (MWM) test was performed to assess the effect on learning and memory. A battery of biochemical estimations was performed following the MWM test such as brain-reduced glutathione (GSH), superoxide dismutase (SOD), thiobarbituric acid reactive species (TBARS), acetylcholinestrase (AChE) activity, and serum cholesterol levels.

Results: Administration of Cu–Ch produced a marked decline in MWM performance measured during the acquisition (78.9?±?3.3) and retrieval trials (9.5?±?2.4), reflecting impairment of learning and memory. Cu–Ch-treated mice also exhibited a marked accentuation of AChE activity (5.8?±?0.55) and TBARS levels (9.74?±?1.9) along with a decline in the GSH level (15.4?±?3.3) and the SOD level (26?±?2.5) when compared with the untreated control group. Administration of clioquinol significantly attenuated Cu–Ch-induced memory deficits and biochemical alterations.

Discussion and conclusion: The findings demonstrate memory restorative ability of clioquinol which may be attributed to its anti-cholinesterase, antioxidative, and cholesterol-lowering potential.     

Aloin: A natural antitumor anthraquinone glycoside with iron chelating and non-atherogenic activities

Abstract

Context: The antitumor activity of aloin, the active anthraquinone of Aloe juice, against different murine and human tumors has been reported.

Objective: In the present study, the impact of repeated aloin treatment at its maximum tolerated dose on serum levels of lipid profile, some elements, iron status and kidney function, compared with doxorubicin (a cardiotoxic anthracycline and inhibitor of erythropoiesis), was assessed.

Materials and methods: Rats were treated with a single dose of doxorubicin (30?mg/kg body weight, intraperitoneal) or aloin (50?mg/kg body weight, intramuscular) twice weekly over 2 weeks.

Results: Acute doxorubicin treatment elevated serum levels of triacylglycerols (59.90%), total cholesterol (42.29%), cholesteryl esters (54.75%), low density lipoprotein–cholesterol (230.16%), very low density lipoprotein–cholesterol (56.42%), urea (287.53%), and creatinine (85.38%), whereas serum high density lipoprotein–cholesterol, sodium, and calcium levels were reduced (44.61, 9.61, and 9.76%, respectively), as compared with controls. In contrast, aloin treatment showed insignificant changes in all the aforementioned parameters. Both doxorubicin and aloin induced erythropoiesis impairment demonstrated by a reduction in blood hemoglobin concentration. While aloin treatment elevated serum iron level (30.28%), doxorubicin treatment reduced serum levels of iron (51.47%) and percent transferrin saturation (55.21%), and in contrast, increased serum total iron binding capacity (34.85%). The chelating affinities of iron-aloin and -doxorubicin complexes, which contain bidentate iron-binding moieties, have been shown in the infrared spectra.

Discussion and conclusion: The non-cardiotoxic effect of aloin treatment was due to its non-atherogenic and iron-chelating activities, which might also contribute in part to its anti-proliferative activity.     

Evaluation of antioxidant and hepatoprotective effects of white cabbage essential oil

Context: There have been no reports of the extraction of essential oil (EO) from white cabbage [Brassica oleracea L. var. capitata (L.) Alef. f. alba DC. (Brassicaceae)] (Bocfal) or its chemical composition, antioxidant activity, or hepatoprotective effects.

Objective: To extract Bocfal EO, to identify and quantify its chemical components, to assess their antioxidant capacity, and to evaluate the hepatoprotective properties of Bocfal EO.

Materials and methods: Bocfal EO was obtained using hydrodistillation (200?mm Hg/58?°C). The chemical composition was analyzed using GC-MS and was quantified using GC-FID. The antioxidant activity of Bocfal EO and its main constituents was evaluated using TBARS in rat brain homogenates. A Bocfal EO hepatoprotective effect (192?mg/kg) on acute carbon tetrachloride (CT)-induced liver damage was determined in rats using biochemical markers and histological analysis. Diallyl disulphide (DADS) (1?mmol/kg) was used as a control for comparison.

Results: Bocfal EO contained organic polysulphides (OPSs), such as dimethyl trisulphide (DMTS) 65.43?±?4.92% and dimethyl disulphide (DMDS) 19.29?±?2.16% as major constituents. Bocfal EO and DMTS were found to be potent TBARS inhibitors with IC₅₀ values of 0.51 and 3?mg/L, respectively. Bocfal EO demonstrated better hepatoprotective properties than did DADS (p?per se, as observed using histopathology.

Discussion and conclusion: The antioxidant properties of Bocfal EO and DMTS may be the mechanism of hepatoprotective action; the parenchymal disturbances by Bocfal EO or DADS alone may be related to the high doses used.     

Synergistic protective effect of folic acid and vitamin B12 against nicotine-induced oxidative stress and apoptosis in pancreatic islets of the rat

Context: Nicotine is an abundant and most significant component of cigarette smoke. Epidemiological evidence strongly suggests an association between cigarette smoking and pancreatic injury, although effects of smoking on endocrine pancreas are still controversial.

Objective: We examined the impact and underlying mechanisms of action of folic acid and vitamin B₁₂ on nicotine-induced damage in pancreatic islets of rats.

Materials and methods: Male Wistar rats were treated with nicotine (3?mg/kg body weight/d, intraperitonealy) with or without folic acid (36?µg/kg body weight/d, orally) and vitamin B₁₂ (0.63?µg/kg body weight/d, orally) for 21?d. Fasting blood glucose, oral glucose tolerance test, HBA_1c, insulin, oxidative stress parameters, proinflammatory cytokines, and CRP level were measured. Histological evaluation, TUNEL assay, and immunohistochemical staining of NF-κB and caspase-3 were also performed.

Results: Folic acid and vitamin B₁₂ blunted the nicotine-induced impairment in fasting blood glucose (51–56% recovery), HbA_1c (64–76% recovery), oral glucose tolerance, insulin level (23–40% recovery), and islet cell counts (26–74% recovery) in rats. Moreover, folic acid in combination with vitamin B₁₂ also attenuated the nicotine-induced changes in markers of oxidative stress (17–88% recovery), TNF-α (40–99% recovery), and IL-6 level (47–65% recovery), CRP level (59–73% recovery), expression of NF-κB and caspase-3, and apoptosis in pancreatic islet cells.

Discussion and conclusion: The present study shows that folic acid and vitamin B₁₂ supplementation can reduce nicotine-induced impairment in glucose homeostasis and apoptosis and damage of pancreatic islet cells by modulating oxidative stress, levels of proinflammatory cytokines, and expression of NF-κB.     

Intracerebroventricular administration of the (1→6)-β-d-glucan (lasiodiplodan) in male rats prevents d-penicillamine-induced behavioral alterations and lipoperoxidation in the cortex

Context: Lasiodiplodan, an exocellular (1→6)-β-d-glucan of molecular weight >1.4?×?10⁶?Da produced by MMPI strain of Lasiodiplodia theobromae (Pat.) Griffon &; Maubl. (Brotyosphaeriaceae) is known to exhibit anti-proliferative activity on breast cancer cells (MCF-7), anticoagulant activity when sulfonylated, and reduction in transaminase activity when administered in rats.

Objective: The effect of intracerebroventricular (I.C.V) injection of lasiodiplodan on neurotoxicity and behavioural changes induced by d-penicillamine was investigated.

Materials and methods: Twenty-four male Wistar rats were initially separated in groups of six and treated with 0.15?μmol/μL of NaCl (Groups Ct and d-Pen) and 0.01?μg/μL of lasiodiplodan (Groups Las and Las?+?d-Pen). After 15?min, they received 6?μmol/μL of NaCl (Groups Ct and Las) and 2?μmol/μL of d-penicillamine (Groups d-Pen and Las?+?d-Pen). The animal behavior was observed in an open-field test for 60?min. Twenty-four h later, the animals were sacrificed and histopathological analysis and Thiobarbituric acid reactive substances (TBARS) production measurements were performed.

Results: Lasiodiplodan prevented neurotoxicity induced by d-penicillamine significantly reducing the production of TBARS (308%; p?Discussion and conclusion: The reduction of TBARS production and convulsive episodes suggests that the protector effect provided by lasiodiplodan passes thought an antioxidant path, possibly interfering in a cascade of neurochemical events, triggering cell death and convulsive episodes. These results demonstrated that lasiodiplodan can be effective in treating neurotoxicity, and reducing damage triggered by convulsions in neuropathies related to GABAergic system.