Salim A. Dhundasi

Effect of L-ascorbic acid on nickel-induced alterations in serum lipid profiles and liver histopathology in rats.

Nickel exposure greatly depletes intracellular ascorbate and alters ascorbate-cholesterol metabolism. We studied the effect of the simultaneous oral treatment with L-ascorbic acid (50 mg/100 g body weight (BW) and nickel sulfate (2.0 mg/100 g BW, i.p) on nickelinduced changes in serum lipid profiles and liver histopathology. Nickel-treated rats showed a significant increase in serum low-density lipoprotein-cholesterol, total cholesterol, triglycerides, and a significant decrease in serum high-density lipoprotein-cholesterol. In the liver, nickel sulfate caused a loss of normal architecture, fatty changes, extensive vacuolization in hepatocytes, eccentric nuclei, and Kupffer cell hypertrophy. Simultaneous administration of L-ascorbic acid with nickel sulfate improved both the lipid profile and liver impairments when compared with rats receiving nickel sulfate only. The results indicate that L-ascorbic acid is beneficial in preventing nickel-induced lipid alterations and hepatocellular damage.

L-ascorbic acid protects the antioxidant defense system in nickel-exposed albino rat lung tissue.

We studied the effect of oral supplementation with L-ascorbic acid (50 mg /100 g body weight (BW) on nickel sulfate (2.0 mg/ 100 g BW, i.p)-induced lipid peroxidation and histopathology in the lung of Wister strain male albino rats. Lipid peroxide and glutathione levels and the activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), were estimated. Nickel sulfate administration significantly increased the level of lipid peroxides and decreased all antioxidant enzyme activities. Nickel sulfate treatment also induced (a) loss of normal characteristics and architectural organization, (b) inflammation in bronchioles, (c) alveolar congestion, (d) alveolar cell hyperplasia, and (e) congestion in the lumen. The simultaneous administration of L-ascorbic acid and nickel sulfate improved both lipid peroxidation and the histopathology of lung when compared with rats receiving nickel sulfate alone. The results indicate that L-ascorbic acid prevents nickel-induced alteration of antioxidant defense mechanisms and histopathology of lung tissue.

Effect of 1-ascorbic acid on antioxidant defense system in testes of albino rats exposed to nickel sulfate

We studied the effect of oral supplementation with L-ascorbic acid (50 mg/100 g body weight) on nickel sulfate (2.0 mg/100 g body weight, i.p.) induced lipid peroxidation in the testes of Wister strain male albino rats. Testicular lipid peroxide and glutathione (GSH) levels and the activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were estimated. Nickel sulfate treatment significantly increased the level of testicular lipid peroxide and decreased all antioxidant enzymes activities and GSH concentration. Simultaneously treatment of L-ascorbic acid exhibited a possible protective role on the toxic effect of nickel sulfate on testicular lipid peroxide and GSH concentration as well as antioxidant enzymatic defense system.

Effect of garlic (Allium sativum) on nickel II or chromium VI induced alterations of glucose homeostasis and hepatic antioxidant status under sub-chronic exposure conditions

Garlic (Allium sativum) has a profound effect in reducing plasma glucose and increasing serum insulin in diabetic rats. We studied the effect of a garlic extract on nickel- or chromium-induced alteration of plasma glucose and hepatic glycogen levels and anti-oxidant status in rats. Adult male albino rats (n=36) divided into six groups of six animals each were treated as follows: Group I, untreated controls; Group II, fresh aqueous homogenate of garlic; Group III, nickel sulfate; Group IV, nickel sulfate + garlic; Group V, potassium dichromate; Group VI, potassium dichromate + garlic. In Groups IV and VI, the simultaneous administration of garlic abrogated a significant nickel- or chromium-induced increase in plasma glucose and decrease in liver glycogen. Nickel and chromium alone also increased lipid peroxide (LPO) and decreased glutathione levels, as well as the activity of superoxide dismutase (SOD), catalase, and glutathione peroxidase. Simultaneous garlic administration significantly reduced the LPO level and remarkably improved SOD activity. Hence, we postulate that the administration of garlic can prevent nickel II- or chromium VI-induced alterations in blood glucose homeostasis while exerting a hepatoprotective effect on glycogen levels and antioxidant status in male albino rats.

α-Tocopherol ameliorates nickel induced testicular oxidative and nitrosative stress in albino rats.

Abstract Background: Heavy metals generate free radicals and induce oxidative and nitrosative stress with depletion of antioxidants. In this study, we have evaluated the beneficial effects of α-tocopherol against nickel sulfate exposed testicular dysfunction. Methods:We studied the effect of supplementation of α-tocopherol (10 mg/100 g body weight, i.m.) on nickel sulfate (2.0 mg/100 g body weight, i.p.) induced testicular oxidative and nitrosative stress in Wister strain male albino rats. Serum and testicular nitric oxide, L-ascorbic acid and serum α-tocopherol concentrations were evaluated. We also evaluated sperm count, motility and histopathology of testes. Results:Nickel treated rats showed significantly decreased body weight, testicular somatic index, sperm count, sperm motility, serum and testicular L-ascorbic acid concentration and serum α-tocopherol level as compared to their controls. However, simultaneous treatment with nickel sulfate and α-tocopherol produced a remarkable improvement of all the above parameters when compared with treatment with nickel alone. Nickel treated rats also had significantly increased serum and testicular nitric oxide concentrations as compared to their controls. However, simultaneous treatment with nickel sulfate and α-tocopherol significantly decreased nitric oxide concentrations in both serum and testes, respectively, as compared to nickel treatment alone. Histopathology of the testes revealed tortuous seminiferous tubules, loss of spermatogenesis process (>75%), congestion and necrosis in nickel sulfate treated rats, whereas rats simultaneously treated with nickel sulfate and α-tocopherol had almost normal seminiferous tubules and near normal spermatogenesis as compared to nickel alone treated rats. Conclusions: Nickel sulfate treatment causes testicular oxidative and nitrosative stress in albino rats, but simultaneous supplementation of α-tocopherol was found to be beneficial in combating against such stresses.

Hypoglycemic activity of curcumin synthetic analogues in alloxan-induced diabetic rats

Abstract The currently available therapies for type 2 diabetes have been unable to achieve normoglycemic status in the majority of patients. The reason may be attributed to the limitations of the drug itself or its side effects. In an effort to develop potent and safe oral antidiabetic agents, we evaluated the in vitro and in vivo hypoglycemic effects of 10 synthetic polyphenolic curcumin analogues on alloxan-induced male diabetic albino rats. In vitro studies showed 7-bis(3,4-dimethoxyphenyl)hepta-1,6-diene-3,5-dione (4) to be the most potential hypoglycemic agent followed by 1,5-bis(4-hydroxy-3-methoxyphenyl)penta-1,4-dien-3-one (10). Structure activity relationship (SAR) of the tested compounds was elucidated and the results were interpreted in terms of in vitro hypoglycemic activities. Furthermore, oral glucose tolerance test (OGTT) with compounds 4, 10 and reference hypoglycemic drug glipizide showed that compound 4 and glipizide had relatively similar effects on the reduction of blood glucose levels within 2 h. Thus, compound 4 might be regarded as a potential hypoglycemic agent being able to reduce glucose concentration both in vitro and in vivo.

Alteration of chemical behavior of L–ascorbic acid in combination with nickel sulfate at different pH solutions in vitro

OBJECTIVE To evaluate the alteration of chemical behavior of L-ascorbic acid (vitamin C) with metal ion (nickel) at different pH solutions in vitro. METHODS Spectra of pure aqueous solution of L-ascorbic acid (E mark) compound and NiSO4 (H2O) (sigma USA) were evaluated by UV visible spectrophotometer. Spectral analysis of L-ascorbic acid and nickel at various pH (2.0, 7.0, 7.4 and 8.6) at room temperature of 29 °C was recorded. In this special analysis, combined solution of L-ascorbic acid and nickel sulfate at different pH was also recorded. RESULTS The result revealed that λmax (peak wavelength of spectra) of L-ascorbic acid at pH 2.0 was 289.0 nm whereas at neutral pH 7.0, λmax was 295.4 nm. In alkaline pH 8.6, λmax was 295.4 nm and at pH 7.4 the λmax of L-ascorbic acid remained the same as 295.4 nm. Nickel solution at acidic pH 2.0 was 394.5 nm, whereas at neutral pH 7.0 and pH 7.4 were the same as 394.5 nm. But at alkaline pH 8.6, λmax value of nickel sulfate became 392.0 nm. The combined solution of L-ascorbic acid and nickel sulfate (6 mg/mL each) at pH 2.0 showed 292.5 nm and 392.5 nm, respectively whereas at pH 7.0, L-ascorbic acid showed 296.5 nm and nickel sulfate showed 391.5 nm. At pH 7.4, L-ascorbic acid showed 297.0 nm and nickel sulfate showed 394.0 nm in the combined solution whereas at pH 8.6 (alkaline) L-ascorbic acid and nickel sulfate were showing 297.0 and 393.5 nm, respectively. CONCLUSIONS Results clearly indicate an altered chemical behavior of L-ascorbic acid either alone or in combination with nickel sulfate in vitro at different pH. Perhaps oxidation of L-ascorbic acid to L-dehydro ascorbic acid via the free radical (HSc*) generation from the reaction of H2ASc + Ni (II) is the cause of such alteration of λmax value of L-ascorbic acid in the presence of metal nickel.

Hexavalent chromium and its effect on health: possible protective role of garlic (Allium sativum Linn).

Abstract Hexavalent chromium or chromium (VI) is a powerful epithelial irritant and a confirmed human carcinogen. This heavy metal is toxic to many plants, aquatic animals, and bacteria. Chromium (VI) which consists of 10%–15% total chromium usage, is principally used for metal plating (H2Cr2O7), as dyes, paint pigments, and leather tanning, etc. Industrial production of chromium (II) and (III) compounds are also available but in small amounts as compared to chromium (VI). Chromium (VI) can act as an oxidant directly on the skin surface or it can be absorbed through the skin, especially if the skin surface is damaged. The prooxidative effects of chromium (VI) inhibit antioxidant enzymes and deplete intracellular glutathione in living systems and act as hematotoxic, immunotoxic, hepatotoxic, pulmonary toxic, and nephrotoxic agents. In this review, we particularly address the hexavalent chromium-induced generation of reactive oxygen species and increased lipid peroxidation in humans and animals, and the possible role of garlic (Allium sativum Linn) as a protective antioxidant.

Protective effect of Vitamin E (a-tocopherol) on nickel-induced alteration of testicular pathophysiology in alloxan-treated diabetic rats

Background and Aim: Diabetes mellitus is a global problem associated with increased formation of free radicals and decrease in antioxidant potential. Nickel generates free radicals and induces oxidative and nitrosative stress with depletion of antioxidants. Vitamin E is the most effective chain-breaking antioxidant against lipid peroxidation. Therefore, the present study was intended to evaluate the possible protective effect of Vitamin E (α-tocopherol) on oxidative stress in the testis of diabetic rats exposed to nickel. Methods: Diabetes was induced by alloxan monohydrate (15 mg/100 g b.wt, i.p.) in adult male Wistar albino rats. Diabetic rats in respective groups were exposed to nickel sulfate (2.0 mg/100 g b.wt, i.p) and α-tocopherol (10 mg/100 g b.wt, i.m.) alone as well as in combination on alternate days until the tenth doses. Testicular cholesterol and protein, aspartate aminotransferase (AST), alanine aminotransferase (ALT), nitric oxide, and lipid peroxide were evaluated by ultraviolet-visible spectrophotometer. Testicular histopathology was also evaluated. Results: Exposure of diabetes and nickel showed significantly decreased body weight, testicular-somatic index, testicular cholesterol and protein, AST, ALT, nitric oxide, and lipid peroxide levels. Simultaneous α-tocopherol supplementation showed remarkable improvement in all these alterations. We observed damage in testicular architecture with, tortuous seminiferous tubules, foci of congestion, necrosis, loss of spermatogenesis > 75% and loss of germ cell layer in diabetic and nickel-exposed diabetic rats. Testis of simultaneous α-tocopherol supplemented diabetic rats showed many normal seminiferous tubules and normal spermatogenesis (≥50%). Conclusion: Vitamin E (α-tocopherol) supplementation could exert a protective effect on the testis of diabetic rats exposed to nickel by suppressing the increased oxidative stress.

A modified simple method for determination of serum α-tocopherol (vitamin E).

Abstract Background: Vitamin E is one of the important antioxidants linked to regulate various diseases, such as atherosclerosis, hypertension, and male infertility. A relatively simple and economic biochemical modified method has been developed to determine serum α-tocopherol concentration. Methods: The current modified method is based on previous Baker and Frank method and the method of Martinek by using 2,2′-bipyridyl, ferric chloride, and xylene. The complex of ferrous ions generated in this reaction with 2,2′-bipyridyl is determined by using a plain enzyme-linked immunosorbent assay microplate (non-antibody coated) at 492 nm. Results: The standard curve of this new modified method shows a linearity with correlation r=0.997 (concentration vs. absorbance). The absorbance of this color complex is directly proportional to the α-tocopherol concentration. The sensitivity of this new modified method has been compared and correlated with Baker and Frank method by using 15 human samples (r=0.99, p<0.0001). Conclusions: This simple and economic method may be routinely used to analyze α-tocopherol concentration in serum.