Protective effect of lycopene against ochratoxin A induced renal oxidative stress and apoptosis in rats

This study was designed to investigate the possible protective effect of lycopene against the renal toxic effects of OTA. Male Sprague-Dawley rats (<200 g, n = 6) were treated with OTA (0.5 mg/kg/day) and/or lycopene (5 mg/kg/day) by gavage for 14 days. Histopathological examinations were performed and apoptotic cell death in both cortex and medulla was evaluated by TUNEL assay. Besides, biochemical parameters and activities of renal antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), thioredoxin reductase (TrxR)], catalase (CAT), superoxide dismutase (SOD); concentrations of total glutathione (GSH), and malondialdehyde (MDA) levels were measured. OTA treatment was found to induce oxidative stress in rat kidney, as evidenced by marked decreases in CAT (35%) activity and GSH levels (44%) as well as increase in SOD activity (22%) vs control group. Furthermore, TUNEL analysis revealed a significant increase in the number of TUNEL-positive cells in cortex (49%) and medulla (75%) in OTA administrated group compared to control (p < 0.05). Lycopene supplementation with OTA increased GPx1 activity and GSH levels, and decreased apoptotic cell death in both cortex and medulla vs. control. The results of this study showed that at least one of the mechanisms underlying the renal toxicity of OTA is oxidative stress and apoptosis is the major form of cell death caused by OTA. Besides, our data indicate that the natural antioxidant lycopene might be partially protective against OTA-induced nephrotoxicity and oxidative stress in rat.     

Protective role of curcumin in nephrotoxic oxidative damage induced by vancomycin in rats

Vancomycin (VAN) is a glycopeptide antibiotic which is active against gram positive bacteria including methicillin resistant Staphylococci. Free radicals are involved in the pathogenesis of vancomycin-induced nephrotoxicity. Therefore, the present study was conducted to investigate the antioxidant potential of curcumin (CUR) against the nephrotoxicity of vancomycin in male rats. Animals used in this study were divided into four groups; the first group was used as control, the second, third and fourth groups were treated orally with curcumin (200 mg/kg BW/day), vancomycin (200 mg/kg BW/day, i.p.), vancomycin plus curcumin, respectively. Curcumin was administered 2 weeks before and 1 week simultaneously with vancomycin. Results showed that thiobarbituric acid reactive substances (TBARS) in plasma and kidney tissue were significantly increased after vancomycin administration. While, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in plasma and kidney tissue and the content of glutathione (GSH) in kidney tissue were decreased compared to control. Vancomycin significantly increased the levels of urea and creatinine. The presence of curcumin with vancomycin caused reduction in induction levels of TBARS in plasma and kidney, urea and creatinine. It ameliorated vancomycin-induced decrease in the activities of antioxidant enzymes and GSH. The presence of curcumin with vancomycin alleviated its nephrotoxic effects. It can be concluded that curcumin has beneficial influences and could be able to antagonize vancomycin nephrotoxicity.     

Kidney antioxidant status,biochemical parameters and histopathological changes induced by methomyl in CD-1 mice

The widespread of pesticide in public health and agriculture has caused severe environmental pollution and health hazards. Methomyl is used worldwide in agriculture and health programs. Besides its advantages in the agriculture, it causes several toxic effects. In this study, we aimed to investigate the effects of methomyl at different time intervals on lipid peroxidation, reduced glutathione (GSH), total sulfhydryl group (T-SH), antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST) and histopathological changes in mice kidney. Ten CD-1 mice per group were assigned to one of four treatment groups. Group one served as control while groups 2, 3 and 4 were orally treated with 1 mg methomyl/kg BW for 10, 20 and 30 days, respectively. Methomyl significantly increased lipid peroxidation in kidney as compared to control group. Levels of GSH and T-SH and activities of SOD, CAT and GST were found to be decreased. On the other hand, methomyl significantly increased the levels of urea, uric acid and creatinine in serum. The histological examination of kidney revealed damage involving the entire renal nephrons in both 20 and 30 days of methomyl exposure. Severe dilatation of the cortical tissue, congested glomerulus with swelling of the endothelial cells and degeneration of the epithelium cells lining the tubules were observed. In conclusion, the results suggest that methomyl exposure can cause renal damage, oxidative stress, perturbations in antioxidant defense system and histopathologic changes in mice kidney in a time dependent manner.     

Argininic acid alters markers of cellular oxidative damage in vitro: Protective role of antioxidants

We, herein, investigated the in vitro effects of argininic acid on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content and on the activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the blood, kidney and liver of 60-day-old rats. We also verified the influence of the antioxidants (each at 1.0 mM) trolox and ascorbic acid, as well as of N^G-nitro-l-arginine methyl ester (L-NAME) at 1.0 mM, a nitric oxide synthase inhibitor, on the effects elicited by argininic acid on the parameters tested. The liver, renal cortex and renal medulla were homogenized in 10 vol (1:10w/v) of 20 mM sodium phosphate buffer, pH 7.4, containing 140 mM KCl; and erythrocytes and plasma were prepared from whole blood samples obtained from rats. For in vitro experiments, the samples were pre-incubated for 1 h at 37 °C in the presence of argininic acid at final concentrations of 0.1, 1.0 and 5.0 μM. Control experiments were performed without the addition of argininic acid. Results showed that argininic acid (5.0 μM) enhanced CAT and SOD activities and decreased GSH-Px activity in the erythrocytes, increased CAT and decreased GSH-Px activities in the renal cortex and decreased CAT and SOD activities in the renal medulla of 60-day-old rats, as compared to the control group. Antioxidants and/or L-NAME prevented most of the alterations caused by argininic acid on the oxidative stress parameters evaluated. Data suggest that argininic acid alters antioxidant defenses in the blood and kidney of rats; however, in the presence of antioxidants and L-NAME, most of these alterations in oxidative stress were prevented. These findings suggest that oxidative stress may be make an important contribution to the damage caused by argininic acid in hyperargininemic patients and that treatment with antioxidants may be beneficial in this pathology.     

Quercetin protects against oxidative stress-related renal dysfunction by cadmium in rats

The aim of this study was to investigate the possible protective role of the dietary flavonoid quercetin on cadmium (Cd)-induced nephrotoxicity using biochemical and histopathological approaches. In experimental rats oral administration of CdCl₂ (5 mg/kg) for 4 weeks significantly induced renal damage which was evident from the increased levels of serum urea, uric acid and creatinine with a significant (p<0.05) decrease in creatinine clearance. Cd also significantly (p<0.05) decreased the levels of urea, uric acid and creatinine in urine. Cd-induced oxidative stress in kidney tissue was indicated by the increased levels of renal lipid peroxidation markers (thiobarbituric acid reactive substances and lipid hydroperoxides) and protein carbonyl content with a significant (p<0.05) decrease in non-enzymatic (total sulphydryl group, reduced glutathione, vitamin C and vitamin E) and enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and glucose 6-phosphate dehydrogenase (G6PD)). Moreover the kidneys of Cd-treated rats showed tubular necrosis, degeneration, dilation, desquamation, thickening of basement membrane and luminal cast formation. Quercetin treatment markedly attenuated the Cd-induced biochemical alterations in serum, urine and renal tissue. Quercetin also ameliorated the Cd-induced pathological changes when compared with Cd-alone-treated group. These data indicate that the natural dietary antioxidant quercetin might have protective effect against Cd-induced nephrotoxicity and oxidative stress in rats.     

Protective effect of Salvia Miltiorrhizae injection on N(G)-nitro-d-arginine induced nitric oxide deficient and oxidative damage in rat kidney

N(G)-nitro-d-arginine (d-NNA) could convert into N(G)-nitro-l-arginine (l-NNA) in vivo, and kidney is the major target organ. In the chiral inversion process, a number of reactive oxygen species (ROS) were generated and NOS activity was inhibited, which may cause renal damage. Salvia miltiorrhiza (SM), a traditional Chinese drug, was used in the treatment of cardiovascular diseases and chronic renal failure. The aim of the present study was to investigate the kidney damage caused by d-NNA administration for 12 weeks and to evaluate the effects of treatment with SM on d-NNA-induced kidney damage. The rats, induced with d-NNA for period of 12 weeks, showed significant elevation of Blood Urea Nitrogen (BUN), Creatinine (Crea) and MDA levels, and significant decrease of SOD and GSH-Px activities, as compared with control group. In addition, the kidney of rats induced with d-NNA only showed remarkable histopathology, including severe mononuclear cell infiltration, mild tubular dilatation and congestion, and moderate interstitial desmoplasia. After 4 weeks SM treatment, the activity of SOD, GSH-Px and iNOS and the production of NO were significantly higher (P < 0.05), and the levels of BUN, Crea and MDA were significantly lower than that of d-NNA only group (P < 0.05). In addition, treatment with SM showed histopathological protection in tubular dilatation, congestion, mononuclear cell infiltration and interstitial desmoplasia. The present results indicate that the toxicity of d-NNA relates to its ability to generate oxidative stress and upregulate NOS activity in rat kidney. SM probably ameliorates d-NNA-induced nephrotoxicity in rats according to scavenging free radical and upregulating NOS activity.     

Propolis attenuates cobalt induced-nephrotoxicity in adult rats and their progeny

The aim of this study was to evaluate the biochemical changes in cobalt-exposed rats and to investigate the potential role of Tunisian propolis against the cobalt-induced renal damages. Twenty-four pregnant Wistar rats were divided into four groups and were treated as follows: group 1 (control) received distilled water; group 2 received 350 ppm of CoCl₂ in drinking water; group 3 received 350 ppm CoCl₂ in drinking water and a propolis-supplemented diet (1 g/100 g of diet); group 4 received a propolis-supplemented diet (1 g/100 g of diet) without cobalt. In the cobalt group, a significant decrease in body, absolute and relative weights was noted when compared to controls. The administration of cobalt to pregnant rats from the 14th day of pregnancy until day 14 after delivery resulted in an increased level of renal malondialdehyde, a decreased renal content of glutathione and antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase in lactating rats and their pups. A statistically significant increase in plasma urea and creatinine serum levels was seen in treated female rats and their pups. Histopathologically, the cobalt-administration induced degenerative changes in the kidney of lactating rats and their pups. When compared with cobalt-treated rats, those receiving the propolis supplementation (along with cobalt-treatment) had lower malondialdehyde levels, higher antioxidant activities and the cobalt-related histopathological changes in the kidneys were at lower severity.Our results suggested that the propolis might be a potential candidate agent against cobalt-induced nephrotoxicity in adult and juvenile rats when administered to female rats during the late pregnancy and the early postnatal period.     

Prevention of cisplatin induced nephrotoxicity by terpenes isolated from Ganoderma lucidum occurring in Southern Parts of India

Investigations were carried out to determine the protective effect of terpenes isolated from the fruiting bodies of Ganoderma lucidum (Fr) P.Karst against nephrotoxicity caused by the cisplatin, in mice. Intraperitoneal administration of cisplatin (16 mg/kg body wt) resulted in significant nephrotoxicity in mice. Serum urea, creatinine and ALP levels were drastically elevated indicating severe nephrotoxicity . The renal antioxidant defense system such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and concentration of reduced glutathione (GSH) were depleted by cisplatin injection. The oral administration of terpenes at a dose of 100 mg/kg body weight prevented increase in urea, creatinine levels and ALP activity and also maintained the renal antioxidant defense. The Ganoderma terpenes also imparted protection against cisplatin induced renal tissue lipid peroxidation. The results indicated that the total terpenes isolated from G. lucidum possessed significant in vivo antioxidant activity and rendered protection against cisplatin induced nephrotoxicity. The results suggest the potential therapeutic use of Ganoderma terpenes to prevent nephrotoxicity caused during chemotherapy using cisplatin.     

Protective effects of aqueous extract of Artemisia campestris against puffer fish Lagocephalus lagocephalus extract-induced oxidative damage in rats

The aerial parts of Artemisia campestris are often used in Tunisian poisoning cases and are known to possess significant antioxidant activities. The objective of this study is to evaluate the protective effects of an aqueous extract (5 g/l) of A. campestris leaves and stems (AE), on oxidative damages induced by liver extract (LT) from poisonous fish Lagocephalus lagocephalus in wistar rats. AE was found to contain large amounts of K⁺, Na⁺, Ca⁺⁺ and significant antioxidant capacities highlighted by high level of polyphenols and scavenging activities for DPPH and superoxide anion.LT-injected rats (1 ml/100 g body wt) for 10 days showed (1) a reduced appetite and diarrhea resulting in a lower growth rate than controls, (2) a decrease in serum ALT and AST activities suggesting liver functional disorders, (3) an increase of serum urea and creatinine and reduced serum sodium and potassium concentrations highlighting renal insufficiency and (4) an oxidative stress as evidenced by the raise of TBARS and the inhibition of SOD, CAT and GSH-Px activities in liver, kidney and brain tissuesAbsorption of AE as a drink, for 20 days (10 pre-treatment days+10 experiment days) did not lead significant change of studied parameters but prevented all the disorders induced by LT.     

Cobalt chloride induces hepatotoxicity in adult rats and their suckling pups

To assess liver damages in pregnant and lactating rats and in their suckling pups, wistar female rats were given through drinking water 350 ppm of CoCl₂ (157 ppm Co²⁺) from the 14th day of pregnancy until day 14 after delivery. The effects of cobalt chloride on lipid peroxidation levels, antioxidant enzyme activities, lipid profile and histopathology aspects of liver were evaluated. Biochemical results showed that lipid peroxidation increased significantly in Co-treated rats, as evidenced by high liver thiobarbituric acid-reactive substance (TBARS) levels. Alteration of the antioxidant system in treated group was confirmed by the significant decline of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and reduced glutathione (GSH) content in liver of suckling pups and their mothers. Moreover, CoCl₂ exposure induced an increase in the activities of the aspartate transaminase (AST), alanine transaminase (ALT), lactate deshydrogenase (LDH) and bilirubin levels in pups and their mothers while liver LDH activity and plasma albumin level were significantly decreased. On the other hand, cobalt chloride induced a marked hypoglycemia, a significant decline in triglycerides and total cholesterol levels. Histological studies showed an infiltration of mononuclear cells and vascular congestion in liver of pups and their mothers.Based on the present findings, exposure of rats to CoCl₂ during late pregnancy and early postnatal period affects antioxidant enzyme activities and lipid peroxidation indicating liver damage in mothers and their offspring.     

Protective effects of Chlorpromazine and Verapamil against cadmium-induced kidney damage in vivo

Overexposure to cadmium (Cd) can induce kidney damage, which was related to the oxidative damage and disturb intracellular Ca²⁺ homeostasis. Chlorpromazine (CPZ), targeting calmodulin (CaM), and the Ca²⁺ channel blocker Verapamil (Ver) are involved in intracellular Ca²⁺ homeostasis processes. The aim of the study was to investigate the kidney damage caused by Cd administrated for 6 weeks and to evaluate the effects of pre-treatment with either chlorpromazine or verapamil on Cd-induced kidney damage. Thirty-two Wistar rats were divided randomly into 4 groups by weight, i.e., control group, Cd-treated group, and CPZ or Ver pre-treated group. The Cd-treated group rats were subcutaneously (s.c.) injected with 7 μmol CdCl₂/kg body weight/day. The CPZ and Ver pre-treated group rats were intraperitoneally (i.p.) injected with 5 mg CPZ/kg body weight/day, 4 mg Ver/kg body weight/day, respectively, 1 h before the s.c. administration of 7 μmol CdCl₂/kg body weight/day. The control group rats were injected s.c. with saline at the same time. The volume of injection was 2 ml/kg body weight, 5 times per week, for up to 6 weeks. After 6 weeks, Cd concentrations in the renal cortex and urine were significantly higher in Cd-treated group than that in controls. Cd concentrations of the urine in CPZ and Ver pre-treated groups were significantly lower than that in Cd-treated group, but there were no significant changes in the renal cortex. Compared with the controls, urinary NAG, ALP activities, and the levels of GSH, MDA, and the activities of PKC, Na⁺–K⁺-ATPase, and Ca²⁺-ATPase in rats from the Cd-treated group were significantly increased. SOD activity was suppressed by Cd. Urinary NAG activity and the level of GSH and the activities of PKC and Ca²⁺-ATPase in both CPZ and Ver pre-treated groups were significantly lower than that in Cd-treated rats. The present results showed that Cd-induced kidney damage was related to the oxidative damage and disturb intracellular Ca²⁺ homeostasis. Both CPZ and Ver possess some ability to prevent cadmium-induced kidney damage via antioxidative action and by maintaining calcium homeostasis.     

Folic acid induces acute renal failure (ARF) by enhancing renal prooxidant state

Systemic administration of folic acid (FA) in mice was used for studying the pathogenesis associated with acute renal failure (ARF). However, the mechanism by which FA induces ARF remains poorly understood. The present study therefore, was planned to investigate the effect of folic acid administration on prooxidant state and associated ultrastructural changes in renal tissue. Balb/c male mice of 4–6 weeks old were divided into control and two folic acid treatment groups (Groups A and B). The animals in group A were administered intraperitoneal injection of folic acid (100 mg kg^?1 body weight) for a period of 7 consecutive days while the animal in group B were administered a single intraperitoneal dose of folic acid (250 mg kg^?1 body weight). The renal tissues were collected and used for the analyses of lipid peroxidative indices and activities of antioxidant enzymes in renal tissues. To corroborate biochemical findings scanning electron microscopy (SEM) in renal tissue was studied. Folic acid treated animals demonstrated marked renal hypertrophy accompanied by severe impairment of renal function. Glutathione levels (GSH) and antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) levels were significantly decreased and LPO levels increased following FA treatment. SEM results further substantiated the observed biochemical changes as evident by severe inflammation in glomeruli, swelling in primary and secondary pedicels, blebbing in villi, and tremendous deprivation of erythrocytes (RBCs) in FA treated kidneys. The present study therefore suggests that acute administration of folic acid leads to the generation of oxidative stress and altered membrane architecture responsible for folic acid induced ARF.     

Cadmium-induced hepatotoxicity in rats and the protective effect of naringenin

This experiment pertains to the protective role of naringenin against cadmium (Cd)-induced oxidative stress in the liver of rats. Cadmium is a major environmental pollutant and is known for its wide toxic manifestations. Naringenin is a naturally occurring citrus flavonone which has been reported to have a wide range of pharmacological properties. In the present investigation cadmium (5 mg/kg) was administered orally for 4 weeks to induce hepatotoxicity. Liver damage induced by cadmium was clearly shown by the increased activities of serum hepatic marker enzymes namely aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma glutamyl transferase (GGT) and serum total bilirubin (TB) along with the increased level of lipid peroxidation indices (thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides) and protein carbonyl contents in liver. The toxic effect of cadmium was also indicated by significantly decreased levels of enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST)) and non-enzymatic antioxidants (reduced glutathione (GSH), vitamin C and vitamin E). Administration of naringenin at a dose of (50 mg/kg) significantly reversed the activities of serum hepatic marker enzymes to their near-normal levels when compared to Cd-treated rats. In addition, naringenin significantly reduced lipid peroxidation and restored the levels of antioxidant defense in the liver. The histopathological studies in the liver of rats also showed that naringenin (50 mg/kg) markedly reduced the toxicity of cadmium and preserved the normal histological architecture of the tissue. The present study suggested that naringenin may be beneficial in ameliorating the cadmium-induced oxidative damage in the liver of rats.     

Gold nanoparticles ameliorate acetaminophen induced hepato-renal injury in rats

Valuable effects of gold particles have been reported and used in complementary medicine for decades. The aim of this study was to evaluate the therapeutic efficacy of gold nanoparticles (AuNPs) against acetaminophen (APAP) induced toxicity. Albino rats were administered APAP at a dose of 2 g/kg p.o. once only. After 24 h of APAP intoxication, animals were treated with three different doses of AuNPs (50 μg/kg, 100 μg/kg, 150 μg/kg) orally or silymarin at a dose of 50 mg/kg p.o., once only. Animals of all the groups were sacrificed after 24 h of last treatment. APAP administered group showed a significant rise in the AST, ALT, SALP, LDH, cholesterol, bilirubin, albumin, urea and creatinine in serum which indicated the hepato-renal damage. A significantly enhanced LPO and a depleted level of GSH were observed in APAP intoxicated rats. Declined activities of SOD and Catalase, after acetaminophen exposure indicated oxidative stress in liver and kidney. The activities of ATPase and glucose-6-Phosphatase were significantly inhibited after APAP administration. AuNPs treatment reversed all variables significantly towards normal level and was found nontoxic. Thus it is concluded that gold nanoparticles played a beneficial role in reducing acetaminophen induced toxicity and can be used in the development of drug against hepatic as well as renal diseases, after further preclinical and clinical studies.     

Antioxidant effects of Citharexylum spinosum in CCl4 induced nephrotoxicity in rat

The present study was carried out to evaluate the antioxidant effect of the chloroform extract of Citharexylum spinosum (CSCE) (Family: Verbenaceae) leaves in Sprague–Dawley male rats. The different groups of animals were administered with carbon tetrachloride (CCl₄; 20% in olive oil, 2 ml/kg body weight) 7 doses (i.p.) at 48 h interval. The CSCE at the doses of 100 and 200 mg/kg or silymarin at a dose of 50 mg/kg were administered intragastrically after 24 h to the CCl₄ treated rats. The effect of CSCE or silymarin on urine and serum markers (urea, creatinine, creatinine clearance, protein, albumin, urobilinogen and nitrite) was measured in CCl₄-induced nephrotoxicity in rat. Further, the effects on lipid peroxidation (TBARS), enzymatic antioxidants (catalase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase) and non-enzymatic antioxidant glutathione (GSH) were estimated in the kidney samples. The CSCE and silymarin produced significant renal protective effects by restoring the concentration of urine and serum markers. Activity level of antioxidant enzymes and GSH contents were increased while lipid peroxidation (TBARS) was decreased, dose dependently with CSCE and silymarin. Decrease in body whereas increase in kidney weight induced with CCl₄ was restored with CSCE and silymarin. Chemical composition of CSCE indicated the presence of flavonoids, terpenoids, alkaloids and very low amount of saponins. Total flavonoids estimated were (127 ± 14.6) as rutin equivalent mg/g of the extract. From these results, it is suggested that CSCE possesses potent nephroprotective and antioxidant properties.     

Effect of metformin against cisplatin induced acute renal injury in rats: A biochemical and histoarchitectural evaluation

Although cisplatin has been a mainstay for cancer therapy, its use is limited mainly because of nephrotoxicity. Accumulating literature suggest the antioxidant and cytoprotective effect of metformin, a first line antidiabetic drug. With this background, we investigated the effect of metformin on the cisplatin induced nephrotoxicity in rats. A single injection of cisplatin (7.5 mg/kg, i.p.) caused marked renal damage, characterized by a significant increase in blood urea nitrogen (BUN), serum creatinine (Cr) and abnormal histo-architecture of kidney. These were accompanied by significant elevation of malondialdehyde (MDA), total reactive oxygen species (tROS) and caspase-3 levels and decreased antioxidant levels. Metformin treatment significantly attenuated the increase in malondialdehyde and tROS generation and restores the decrease in both enzymatic and non-enzymatic antioxidants. However metformin treatment did not prevent the cisplatin induced renal injury as there was no significant difference of renal function parameters (BUN and Cr), kidney histopathology as well as caspase-3 activity between cisplatin per se and metformin plus cisplatin treated rats. Histopathology studies revealed that similar glomerular and tubular pathological architecture in both cisplatin per se and cisplatin plus metformin group. In conclusion, the present study demonstrated that metformin is not an adjuvant drug to treat nephrotoxicity associated with cisplatin therapy.     

Protective effects of nigella sativa against gentamicin-induced nephrotoxicity in rats

The aim of this study was focused on investigating the possible protective effect of NS against GS-induced nephrotoxicity. Twenty four Wistar-albino rats were divided into four equal groups as follows: control group, GS group (100 mg/kg intraperitoneal – i.p.), NSL+GS group (0.2 ml/kg+100 mg/kg i.p.) and NSH+GS group (0.4 ml/kg+100 mg/kg i.p.). Plasma creatinine and urea levels significantly increased as a result of nephrotoxicity in the GS group. Also, creatinine and urea levels significantly decreased in NSL+GS and NSH+GS groups. In the GS group, plasma MDA and NO levels increased significantly (p<0.05) and erythrocyte SOD and GSH-Px activities decreased significantly (p<0.05) when compared with control group. NS administration with GS injection resulted in significantly decreased MDA and NO generation and increased SOD and GSH-Px activities when compared with GS group. Proximal tubular necrosis, vacuolation, desquamation and degeneration in epithelial cells of the proximal tubules, hyaline casts in tubular lumen, mononuclear cell infiltration, glomerular and basement membrane alterations were histopathologically detected in the kidneys of the GS group. Co-treatments with NS (low and high dose) considerably decreased the renal damage when compared with the GS group. In conclusion, NS acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GS both in the biochemical and histopathological parameters.     

Oral acute toxicity study as well as tissues oxidative stress and histopathological disorders in edible camphor administered rats

In the South-western part of Nigeria, edible camphor (EC) infusions are used to treat pile, back pain, and erectile dysfunction, especially in preparation for sexual intercourse. We therefore carried out oral acute toxicity study, and then investigated the effects of various doses of EC on the activities of lactate dehydrogenase (LDH), catalase (CAT), and superoxide dismutase (SOD), as well as reduced glutathione (GSH) and malondialdehyde (MDA) levels in wistar rats. Oral LD₅₀ of EC was estimated to be 9487 mg/kg body weight. Based on this, thirty animals were divided into six groups of five rats each, and were orally administered various doses of EC (1, 2, 4, and 6 g/kg body weight) for seven days. Comparing all results with control, EC significantly increased serum LDH activity (4 and 6 g/kg), liver (6 g/kg) and kidney (4 and 6 g/kg) MDA levels, as well testis GSH levels (1 g/kg). CAT activities were significantly decreased in liver, kidney, and testis, and also lung GSH level by all the tested doses. For SOD, activities were significantly increased in liver and lung, but significantly decreased in kidney (2, 4, and 6 g/kg). Various pathological disorders were also seen following the various doses of EC administered, especially in liver, kidney and lung. Therefore, from our findings, it is evident that incessant, misuse or overconsumption of EC could lead to oxidative tissue damage in rats.     

Ethanol induced adaptive changes in blood for the pathological and toxicological effects of chronic ethanol consumption in humans

Alcohol consumption is associated with a number of toxicological changes in blood and the oxidant–antioxidant system. The present study was performed to investigate the alcohol induced toxicological, pathological changes in blood and an adaptive role of erythrocyte antioxidant system in chronic alcoholics. Human male volunteers aged 44 ± 6 years with similar dietary habits were divided into two groups, namely non-alcoholic controls and chronic alcoholics. We measured hematological parameters, erythrocyte lipid peroxidation, NO production, erythrocyte antioxidant and liver function test enzyme activities. Alcoholics had increased erythrocyte nitric oxide levels and also elevated erythrocyte lipid malondialdehyde (MDA) concentrations. Strikingly, increments in reduced glutathione and markedly increased activities of certain antioxidant enzymes such as glutathione reductase (GR), superoxide dismutase (SOD), and another related enzyme G-6 phosphate dehydrogenase (G6-PDH) with no alterations in the activities of glutathione S-transferase (GST), glutathione peroxidase (GPx), and catalase (CAT) in chronic alcoholics were observed compared to controls. Furthermore, erythrocyte NO levels were positively correlated with lipid peroxidation, SOD, GSH, GR and G6PDH in chronic alcoholics. In addition, increased AST/ALT ratio and a significant increase in WBC and platelets were also noticed. Together, these results indicate that, antioxidants and defense enzymes appear to be rendering protection as a consequence of chronic adaptation in alcoholics.     

Hepatoprotective role and antioxidant capacity of selenium on arsenic-induced liver injury in rats

The present study was undertaken to evaluate the protective effect of selenium against arsenic-induced oxidative damage in experimental rats. Males were randomly divided into four groups where the first was served as a control, whereas the remaining groups were respectively treated with sodium selenite (3 mg/kg b.w.), sodium arsenite (5.55 mg/kg b.w.) and a combination of sodium arsenite and sodium selenite. Changes in liver enzyme activities, thiobarbituric acid reactive substances (TBARS) level, antioxidants and reduced glutathione (GSH) contents were determined after 3 weeks experimental period.Exposure of rats to As caused a significant increase in liver TBARS compared to control, but the co-administration of Se was effective in reducing its level. The activities of glutathione peroxidase (GPx) and glutathione-S-transferase (GST) of As-treated group were found lower compared to the control and the Se-treated group. The co-administration of Se had an additive protective effect on liver enzyme activities compared to As-treated animals. On the other hand, a significant increase in plasmatic activities of AST, ALT and ALP was observed in As-treated group. The latter was also exhibited a decrease in body weight and an increase in liver weight compared to the control. The co-administration of Se has decreased the activities of AST, AST and ALP and improved the antioxidant status as well. Liver histological studies have confirmed the changes observed in biochemical parameters and proved the beneficial role of Se. To conclude, results suggest that As exposure enhanced an oxidative stress by disturbing the tissue antioxidant defense system, but the Se co-administration protected liver tissues against As intoxication probably owing to its antioxidant properties.