Protective effect of gallic acid against lindane induced toxicity in experimental rats

Lindane is an organochlorine pesticide that persists in the environment, bioaccumulate through food chain and has a risk of causing adverse effects to human health and the environment. It induces cell damage by producing free radicals and reactive oxygen species. The aim of the present study is to investigate the protective effect of gallic acid (a plant derived polyphenol) against lindane induced hepatic and renal toxicity in rats. Liver damage was assessed by hepatic serum marker enzymes like SGOT, SGPT and ALP and histopathological observation. Renal damage was observed by histopathological examination and serum markers like creatinine and urea. Treatment with lindane increased the levels of lipid peroxidation, serum marker enzyme activity with a concomitant decrease in GSH, CAT, SOD, GPx and GST. Histological alterations were also observed in kidney and liver tissue with lindane treatment. Co-treatment of gallic acid significantly prevented the lindane induced alterations in kidney and liver tissues with a decrease in LPO, serum marker enzyme activity and a significant increase in antioxidant levels. These results suggest that gallic acid has protective effect over lindane induced oxidative damage in rat liver and kidney.     

Twenty-eight days repeated oral dose toxicity study of gemifloxacin in Wistar albino rats

The purpose of this study was to investigate the potential toxicity of gemifloxacin by 28-day repeated oral dose in Wistar albino rats. The test article, was administered daily by gavage to male and female rats at dose levels of 0, 50, 100, 200 mg/kg/day. At the end of treatment period, 12 rats/sex/group was sacrificed, while six extra rats/sex in the vehicle control and highest dose groups sacrificed after 14 days recovery period. During the treatment and recovery periods, clinical signs, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, phototoxicity, hematology, serum biochemistry, synovial fluid biochemistry, electrocardiogram (ECG), gross findings, organ weights, microscopic examination of synovial fluid, and histopathology were examined. Hematological and serum biochemical investigations revealed a dose-dependent increase in the total white blood cell (WBC), total bilirubin (T-BIL), glucose (GLU), alanine aminotransferase (ALT) and significant decreases in total protein (TP) were observed in both sexes at the same dose, at the end of treatment period, but the levels returned toward normal during the recovery period. Histopathology of talar joint showed that erosion of the articular surface of that joint in both sexes at the end of treatment period at the dose level of 200 mg/kg/day. Degenerative changes in tendinocytes were observed in Achilles tendon of both sexes at the high dose level at the end of treatment period. In histopathological study shows partial effacement of liver architecture and focal ulceration in gastric mucosa at the high dose level at the end of treatment period. Based on these results, it was concluded that 28 days repeated oral dose of gemifloxacin caused increases in the liver weight, WBC count, T-BIL, glucose level, ALT, decreasing the TP, cause chronic hepatitis and acute gastritis, erosion of the articular surface of joint and histopathologic changes in Achilles tendon in rats at the dose level of 200 mg/kg/day.     

Immunomodulatory activity of Asparagus racemosus on systemic Th1/Th2 immunity: Implications for immunoadjuvant potential

Ethnopharmacological relevance

Roots of Asparagus racemosus Willd (Shatavari in vernacular) are widely used in Ayurveda as Rasayana for immunostimulation, galactogogue as also in treatment of conditions like ulcers and cancer. Various studies have indicated immunomodulatory properties of Shatavari root extracts and formulations.

Aim of the study

To study the effect of standardized Asparagus racemosus root aqueous extract (ARE) on systemic Th1/Th2 immunity of SRBC sensitized animals.

Materials and methods

We used HPTLC to quantify steroidal saponins (Shatavarin IV, Immunoside^®) and flow cytometry to study effects of ARE on Th1/Th2 immunity. SRBC specific antibody titres and DTH responses were also monitored as markers of Th2 and Th1 responses, respectively. We also studied lymphocyte proliferation. Cyclosporin, cyclophosphamide and levamisole were used as controls.

Results

Treatment with ARE (100 mg/(kg b.w. p.o.)) resulted in significant increase of CD3⁺ and CD4/CD8⁺ percentages suggesting its effect on T cell activation. ARE treated animals showed significant up-regulation of Th1 (IL-2, IFN-g) and Th2 (IL-4) cytokines suggesting its mixed Th1/Th2 adjuvant activity. Consistent to this, ARE also showed higher antibody titres and DTH responses. ARE, in combination with LPS, Con A or SRBC, produced a significant proliferation suggesting effect on activated lymphocytes.

Conclusion

The study suggests mixed Th1/Th2 activity of ARE supports its immunoadjuvant potential.     

Anti-arthritic potential of marine macroalgae Turbinaria ornata in Complete Freund’s Adjuvant induced rats

T. ornata a macroalgae rich in bioactive molecules possess various biological activities. Herein, the aim of the study is to evaluate the aqueous extract and the sulphated polysaccharide isolated from T. ornata for its anti-arthritic potential in Complete Freund’s Adjuvant (CFA) induced arthritis in rats. Anti-arthritic potential of aqueous T. ornata (ATO) and T. ornata sulphated polysaccharide (TSP) was evidenced by the significant reduction in paw volume and arthritic score. Inflammatory and antioxidant markers were found to be restored in the drug treated groups which was found to be in line with dexamethasone a standard anti-inflammatory drug. The histopathological and radiological examination adds on the support to the above findings confirming the anti-arthritic potential of ATO and TSP. It is interesting to note that the sulphated polysaccharide inhibits inflammation and bone damage at very low dose itself. Hence, TSP could be considered as a better candidate in the management of chronic inflammatory diseases like rheumatoid arthritis.     

Efficacy of Adiantum capillus veneris Linn in chemically induced urolithiasis in rats

Ethnopharmacological relevance: Adiantum capillus veneris Linn has been recommended in ancient literature of Unani system of medicine as an important ingredient of many formulations for the treatment of urolithiasis. Its decoction has long been used for the same purpose by several Unani physicians.     

Inhibition of pancreatic lipase, α-glucosidase, α-amylase,and hypolipidemic effects of the total flavonoids from Nelumbo nucifera leaves

Ethnopharmacological relevance

Nelumbo nucifera Gaertn. leaves have been used as medicinal herbs in the past 1300 years, specifically utilized to cure hyperlipidemia, hyperglycemia, and obesity. It has been recorded in the most famous medicinal book in China for more than 400 years. The present study aims to identify the potential therapeutic activities of the flavonoids isolated from Nelumbo nucifera leaves.

Materials and methods

Nelumbo nucifera leaf flavonoids (NLF) were tested for the inhibition of lipase, α-glucosidase, and α-amylase activities in vitro. A single dose of NLF was administered by oral gavage in mice for acute toxicity. Wistar rats with high-fat diet-induced hyperlipidemia and two other animal models were used to evaluate the hypolipidemic effects of NLF.

Results

Our in vitro biochemistry tests revealed that the NLF showed high inhibitory activity against porcine pancreatic lipase, α-amylase, and α-glucosidase with IC₅₀ values of 0.38±0.022, 2.20±0.18, and 1.86±0.018 mg/mL, respectively. Furthermore, the NLF significantly lowered the lipid components, such as the total cholesterol, triglycerides, low-density lipoprotein cholesterol, and malondialdehyde, in various established in vivo systems and raised the high-density lipoprotein cholesterol. Moreover, the NLF alleviated high-fat diet-induced lipid accumulation in the liver.

Conclusions

The results demonstrate that NLFs can effectively ameliorate hyperlipidemia and inhibit the key enzymes related to type 2 diabetes mellitus. Our findings may provide new pharmacological basis for the treatment of hyperlipidemia, hyperglycemia, and obesity using NLFs.     

Development of safety profile evaluating pharmacokinetics, pharmacodynamics and toxicity of a combination of pioglitazone and olmesartan medoxomil in Wistar albino rats

Pioglitazone (PIO), an antidiabetic drug and olmesartan medoxomil (OLM), an antihypertensive drug were administered orally alone and in combination to Wistar albino rats for evaluation of pharmacokinetics, pharmacodynamics and repeated dose 28-day oral toxicity of individual drugs and their combination. Pharmacokinetic study was performed by orally administering PIO and OLM at single dose of 3 and 2mg/kg, respectively alone and in combination analyzing the plasma samples using LC-MS/MS. Antidiabetic activity evaluation was done in type-2 diabetes mellitus induced animals at same dose level as in pharmacokinetic study daily for 30 days. PIO and/or OLM were administered orally to animals at daily doses of 50, 100 and 150 mg/kg for 28 days for toxicity study. There was no significant alteration in the pharmacokinetic parameters of either drug indicating absence of any pharmacokinetic interaction when co-administered. Positive pharmacodynamic interaction between PIO and OLM was established in this study. Two drugs in combination showed no evidence of potentiation of 28-day repeated dose toxicity in animals. Again, drugs, alone and in combination, caused only minor changes in clinical-laboratory tests and histopathological change was not found in the experiment performed. In conclusion, PIO and OLM combination can primarily be stated as safe in terms of present toxicity and pharmacokinetics findings.     

Salutary effect of NFκB inhibitor and folacin in hyperhomocysteinemia-hyperlipidemia induced vascular dementia

Dementia of vascular origin or vascular dementia (VaD) is considered as the second commonest form of dementia after Alzheimer's disease (AD). In the last ten years various researchers have reported a strong association of hyperhomocysteinemia (HHcy), hyperlipidemia (HL) and dementia. This study investigates the salutary effect of natrium diethyl dithio carbamate trihydrate (NDDCT), a nuclear factor-kappaB (NF-κB) inhibitor as well as folacin (Vitamin-B(9)) in HHcy-HL induced VaD. l-methionone was used to induce HHcy-HL and associated VaD. Morris water-maze (MWM) was used for testing learning and memory. Vascular system assessment was done by testing endothelial function. Biochemical estimations were performed to assess HHcy (serum homocysteine), HL (serum cholesterol), oxidative stress (aortic superoxide anion, serum and brain thiobarbituric acid reactive species and brain glutathione), nitric oxide levels (serum nitrite/nitrate) and cholinergic activity (brain acetyl cholinesterase activity). L-methionine treated animals have shown HHcy-HL, endothelial dysfunction, impairment of learning, memory, reduction in serum nitrite/nitrate levels and brain glutathione (GSH) along with increase in serum and brain thiobarbituric acid reactive species (TBARS), and brain acetylcholinesterase activity. NDDCT, folacin and donepezil (positive control) significantly improved HHcy-HL induced impairment of learning, memory, endothelial dysfunction, and changes in various biochemical parameters. l-methionine induced HHcy-HL has caused VaD development in rats. NFκ-B inhibitors and folacin may be considered as potential agents for the management of HHcy-HL induced VaD.     

Hepatoprotective and antioxidant effects of Commiphora berryi (Arn) Engl bark extract against CCl(4)-induced oxidative damage in rats.

Oxidative damage is involved in the pathogenesis of various hepatic injuries. In the present study the capacity of Commiphora berryi (Arn) Engl bark as an antioxidant to protect against CCl(4)-induced oxidative stress and hepatotoxicity in Albino Wistar rats was investigated. Intraperitoneal injection of CCl(4), administered twice a week, produced a marked elevation in the serum levels of aspartate transaminase, alanine transaminase, alkaline phosphatase and bilirubin. Histopathological analysis of the liver of CCl(4)-induced rats revealed marked liver cell necrosis with inflammatory collections that were conformed to increase in the levels of SOD, GPx and CAT. Daily oral administration of methanolic extract of C. berryi (Arn) Engl bark at 100 and 200mg/kg doses for 15 days produced a dose-dependent reduction in the serum levels of liver enzymes. Treatment with C. berryi normalized various biochemical parameters of oxidative stress and was compared with standard Silymarin. Therefore, the results of this study show that C. berryi (Arn) Engl bark can be proposed to protect the liver against CCl(4)-induced oxidative damage in rats, and the hepatoprotective effect might be correlated with its antioxidant and free radical scavenger effects.     

In vivo efficacy and pharmacokinetics of bi-aryl oxazolidinone RBx 11760 loaded polylactic acid–polyethylene glycol nanoparticles in mouse hematogenous bronchopneumonia and rat groin abscess caused by Staphylococcus aureus

RBx 11760 is a bi-aryl oxazolidinone antibacterial agent active against Staphylococcus aureus but has poor solubility. Here we have encapsulated RBx 11760 in PLA–PEG NPs with an aim to improve physicochemical, pharmacokinetics and in vivo efficacy. The average size and zeta potential of RBx 11760 loaded NPs were found to be 106.4 nm and ?22.2 mV, respectively. The absolute size of nanoparticles by HRTEM was found to be approximately 80 nm. In vitro antibacterial agar well diffusion assay showed clear zone of inhibition of bacterial growth. In pharmacokinetic study, nanoparticle showed 4.6-fold and 7-fold increase in AUC_inf and half-life, respectively, as compared to free drug. RBx 11760 nanoparticle significantly reduced bacterial counts in lungs and improved the survival rate of immunocompromised mice as compared to free drugs. Thus, RBx 11760 loaded nanoparticles have strong potential to be used as nanomedicine against sensitive and drug resistant Staphylococcus aureus infections.