Genotoxic And Cytotoxic Effects Of Oral Vanadyl Sulphate.

BACKGROUND: Vanadyl sulphate is available as herbal medicine against diabetes mellitus and body building supplement, over the counter worldwide. The available data on its safety is controversial and inadequate. The objective of this study was to analyse its safety in usual therapeutic dose range. METHODS: It was an experimental study carried out at the Department of Biochemistry & Molecular Biology, Army Medical College, National University of Medical Sciences (NUMS), Rawalpindi, Pakistan, from Jun 2014 to Oct 2018. The study was carried out on 105 Sprague Dawley rats for duration of 24 weeks. The animals were randomly distributed in three groups of 35 each. The group I rats were marked as control while rats of group II & III were administered vanadyl sulphate 0.06mg/day and 0.3mg/day respectively. Alanine amino transferase (ALT) and Malondialdehyde (MDA) were measured in serum while comet assay was performed on WBCs. RESULTS: The plasma levels of ALT and MDA were significantly raised in group II and III subjects. Single cell gel electrophoresis (SCGE) / comet assay showed minimal "tail moment" in control group and increased tail moment in group II and III in a dose dependent manner which indicates dsDNA breaks. CONCLUSIONS: It was observed that vanadyl sulphate causes hepatocellular toxicity, oxidative stress and damage to the DNA in usual therapeutic/ supplemental doses. Due to hazardous effects, its use in humans as alternate medicine may be reviewed.

Effects of oral vanadium on glycaemic and lipid profile in rats.

OBJECTIVE: Vanadyl sulphate, an inorganic tetravalent salt of transition metal vanadium is conventionally used to treat diabetes and by athletes as body-building supplement. Vanadyl sulphate is a constituent of many supplements and herbal preparations available over the counter in many parts of the world. In this study the efficacy of the salt as hypoglycaemic agent and its effects on lipid profile were determined when administered in therapeutic dose range (in humans) to healthy Sprague Dawley rats for a considerable duration. METHODS: One hundred and five rats were randomly divided into three groups of 35 rats each. Animals of all three groups were provided normal rodent diet and water ad libitum. Group I animals were administered 0.5 ml plain water through oral gavage while group II and group III rats, 0.25mg/Kg/day and 1.2mg/Kg/day vanadyl sulphate respectively for 24 weeks. At the end of 24 weeks intra-cardiac blood sampling was done and blood glucose, insulin and lipid profile were measured. RESULTS: There was significant decrease in plasma glucose, insulin and HDL-c levels while LDL-c, TGs and TC levels were significantly increased in a dose dependent manner in treated groups. CONCLUSIONS: Our study showed that vanadyl sulphate possesses hypoglycaemic effect in healthy rats while insulin levels are also decreased which may be secondary to hypoglycaemia. Moreover it causes unfavorable derangement of lipid parameters in treated rats. In conclusion vanadyl sulphate though contains significant hypoglycaemic effects; its use in humans may be re-evaluated to establish its safety in relation to lipid profile.

Comparison Of Protective Effect Of Green Tea And Vitamin C Against Cypermethrin Induce Nephrotoxicity In Mice.

BACKGROUND: Insecticide toxicity is the problem of every person in under developed countries. It is necessary to counteract its effect by natural and cheap remedies like green tea and vitamin C. In this manner common man can also enjoy blessings of life. The current research was performed to compare the protective function of green tea and vitamin C on experimental cypermethrin provoked nephrotoxicity. METHODS: Forty healthy Balb/C mice purchased from National Institute of Health, Islamabad, Pakistan and divided in to four groups (10 each). Group a was control which received only normal diet. Group B, group C and group D were experimental groups which were given Cypermethrin, Cypermethrin with green tea and Cypermethrin with vitamin C respectively. These groups were also given normal diet. After 1 month blood was drawn by intra-cardiac method to assess renal parameters. RESULTS: One month research showed increase in serum urea to 6.8±.48 m.mol/l (n=3.9±.44) while green tea and vitamin C normalize them to 4.0±.83m.mol/l and 3.4±.33m.mol/l respectively. Serum creatinine increased to 42.90±3.28m.mol/l (n=29.50±3.95) while green tea and vitamin C normalize them to 28.80±4.58m.mol/l and 22.60±2.06m.mol/l correspondingly. CONCLUSIONS: The results showed that green tea and vitamin C neutralized toxicity induced by Cypermethrin in mice and their effect is comparable.

Comparative evaluation of Nigella sativa (Kalonji) and simvastatin for the treatment of hyperlipidemia and in the induction of hepatotoxicity.

Hyperlipidemia is a major risk factor for incidence of coronary artery disease. Simvastatin is a synthetic lipid lowering drug and Nigella sativa seeds found helpful in controlling hyperlipidemia. The study performed to evaluate the efficacy of Nigella sativa in comparison to simvastatin to treat hyperlipidemia. Thirty Sprague Dawley rats fed on an ad libitum diet for 02 weeks, on cholesterol diet for 08 weeks. Then group II treated with simvastatin and group III with Nigella sativa for 06 weeks. Blood samples analyzed for serum cholesterol, serum triglycerides, HDL-C, LDL-C & serum ALT. The results evident that Nigella sativa (kalonji) and simvastatin showed significant improvement in the lipid profile of rats in respective groups after treatment. The p value <0.05 of group II and III documented that Nigella sativa (kalonji) affect the lipid profile in the same way as of simvastatin. However, ALT levels significantly raised in group II treated with simvastatin compared to group III. Nigella sativa and simvastatin showed comparable effects in the treatment of hyperlipidemia. Nigella sativa showed protective role in terms of hepatic dysfunction and can be used as a cholesterol lowering agent.

Effect of ascorbic acid and alpha tocopherol supplementation on acute restraint stress induced changes in testosterone, corticosterone and nor epinephrine levels in male Sprague Dawley rats.

BACKGROUND: Stress of various origins suppresses male reproductive functions through releasing stress hormones. Antioxidant like ascorbic acid (AA) and alpha tocopherol (AT) have been thought to protect the body against stress induced damage. Whether, these antioxidants confer protection against the stress induced increased levels of corticosterone and nor-epinephrine, and decreased testosterone secretion have been investigated in this study. METHODS: This quasi experimental study was carried out at the Department of Physiology, Army Medical College Rawalpindi in collaboration with National Institute of Health, Islamabad during March to September 2009. Eighty male Sprague Dawley rats were divided into five groups with sixteen rats in each group. Group-I served as the control without stress while group-II was exposed to restraint stress for 6 hours, group-III was administered AA, group-IVAT and group-V was supplemented with both the antioxidants along with standard diet for one month. All antioxidant supplemented groups were exposed to restraint stress for 6 hours. Immediately after the stress episode, blood sample was obtained for the assay of serum testosterone, serum corticosterone by EIA and plasma nor-epinephrine levels by ELISA. Data were analyzed on SPSS-13 and p-value less than 0.05 was considered significant. RESULTS: Acute restraint stress resulted in a statistically significant rise in corticosterone and nor-epinephrine levels and fall in serum testosterone levels. AA supplementation for one month revealed insignificant changes in stress induced hormonal parameters. AT alone and in combination with ascorbic acid prevented the fall in testosterone level as well as rise in corticosterone, however nor-epinephrine levels remained unchanged. CONCLUSION: Supplementation with AT alone or in combination with AA prevent reduction in testosterone and rise in corticosterone levels while keeping the nor-epinephrine levels unchanged after acute restraint stress in Sprague Dawley rats.

Impact of CYP2C9 genetic polymorphism on warfarin dose requirements in Pakistani population.

Variations of cytochrome-P450 enzyme system (CYP2CP) are associated with impaired metabolism of warfarin. The objective of our study was to estimate the frequency of genetic and allelic variants of CYP2C9 in Punjabi population of Pakistan and their effects on warfarin dose requirement. One hundred and twenty unrelated Pakistani subjects belong to Punjab province, were randomly included from the registry of National Institute of Heart Disease Rawalpindi, Pakistan. The patients had stable international normalized ratio (INR) of 2 to 3 for last 3 months with warfarin therapy after heart valves replacement. The detection of CYP2C9 variant was done on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Total 120 patients (73 males; 47 females) of mean age of 37 years participated in the study. Nine patients had mutant allele CYP2C9*3 (7.5%), one CYP2C9*2 (0.8%) and 110 patients exhibited wild type CYP2C9*1 (91.7%). The frequency of CYP2C9 genotype was *1/*1 (0.858) ; *1/*3 (0.117) ; 2/*20 (0.08 ) and *3/*3 (0.017) in our study population. A high dose of warfarin (42.2+9.56) mg/week is required for patients with *1/*1 genotype as compared to patients with *2/*2 (17.5+1.9) and *1/*3 (16.6+2.3) allele (p<0.001). Individuals with CYP2C9*3/3* need lowest (8.75±1.76 mg/week) daily warfarin dose. In conclusion, the genetic variations in the CYP2C9 occur in 14% of Punjabi ethnic group in Pakistan. Presence of CYP2C9*2 or *3 variants is an independent predictor of low warfarin dose requirement in our patients. CYP2C9 variants assay may be used in high risk groups for appropriate dose adjustment to avoid complications on long term basis.

Effect of thiamine on lipid profile in diabetic rats.

OBJECTIVE: To determine the effect of high dose thiamine on dyslipidemia in diabetic rats. STUDY DESIGN: Experimental interventional study. PLACE AND DURATION OF STUDY: The Animal House/Laboratory of the National Reference Laboratory for Poultry Diseases (NRLPD)/Biochemistry Department, Army Medical College, Rawalpindi, from December 2006 to January 2007. METHODOLOGY: The study was conducted on 120, 12 weeks old male albino rats of Sprague Dawley Strains randomly divided into 4 groups of 30 rats each. Group I comprised of 30 normal rats, on normal (regular) diet. Group II comprised of 30 diabetic rats, on normal (regular) diet. Group III comprised of 30 normal rats, on thiamine supplemented diet. Group IV comprised of 30 diabetic rats, on thiamine supplemented diet. Out of the 120 rats, 60 were made diabetic by injecting Alloxan. Blood glucose levels were measured by applying glucose oxidase method. Determination of total HbA1c, triglyceride, HDL (High Density Lipoproteins) and total cholesterol was performed by diagnostic kits. The significance of difference in mean values of study groups (glycemia and lipid profile) was assessed by applying ANOVA and independent Student's t-test. RESULTS: Significant difference was found in the levels of triglycerides, cholesterol and LDL in the diabetic rats on supplemented diet p < 0.05, but no significant difference was noticed in the value of glycosylated Hb (HbA1c) (p>0.05) of all the 4 groups. CONCLUSION: Thiamine corrected dyslipidemia but not hyperglycemia in diabetic rats.