Effect of rosuvastatin on obesity-induced cardiac oxidative stress in Wistar rats—A preliminary study.

The prevalence of obesity has been rising alarmingly and it has now become a global concern causing an enormous economic burden on the health care system. Obesity is generally linked to complications in lipid metabolism and oxidative stress. The aim of the present study was to investigate the effect of rosuvastatin (10 mg/kg, po) on obesity-induced oxidative stress in high fat-fed Wistar rats. Oral administration of rosuvastatin (10 mg/kg) for 21 days along with high fat diet brought about significant elevation in serum high density lipoprotein and cardiac antioxidant enzymes levels (superoxide dismutase, catalase, glutathione, glutathione peroxidase, glutathione peroxidase-, glutathione reductase- and glutathione-S-transferase) while decreasing in serum lactate dehydrogenase, apolipoprotein-B, lipids (triglycerides, total cholesterol, low density lipoprotein-cholesterol, very low density lipoprotein-cholesterol and atherogenic index) and cardiac thiobarbituric acid reactive substances levels. The results were comparable with orlistat, a standard antiobesity drug. These preliminary results for the first time demonstrate that administration of rosuvastatin can be beneficial for the suppression of obesity-induced oxidative stress and dyslipidemia in high fat-fed Wistar rats.

Effect of Aloe vera (Aloe barbadensis Miller) gel on doxorubicin-induced myocardial oxidative stress and calcium overload in albino rats.

Administration of a single dose of doxorubicin (DOX) (7.5 mg/kg, iv) produces cardiotoxicity, manifested biochemically by significant decrease in blood glutathione (GSH) and tissue GSH along with elevated levels of serum lactate dehydrogenase (LDH) and serum creatine phosphokinase (CPK). In addition, cardiotoxicity was further confirmed by significant increase in lipid peroxides expressed as malondialdehyde (MDA, secondary indicator of lipid peroxidation), tissue catalase and tissue superoxide dismutase (SOD). Administration of A. vera gel (100 and 200 mg/kg) orally for 10 days produced a significant protection against cardiotoxicity induced by DOX evidenced by significant reductions in serum LDH, serum CPK, cardiac lipid peroxides, tissue catalase and tissue SOD along with increased levels of blood and tissue GSH. The results revealed that A. vera gel produced a dose dependent protection against DOX induced cardiotoxiaty.

Causality assessment of suspected adverse drug reaction with anti-tubercular therapy by WHO probability scale.

The objectives of the study is to monitor and causality assessment of suspected ADRs by WHO Probability Scale in patients of tuberculosis undergoing treatment with anti-tuberculous drugs. An Open, Non- Comparative Study was carried out in the Medicine Department of Majeedia Hospital, Jamia Hamdard, over a period of 6 months. A total of 139 patients, satisfying Inclusion and Exclusion Criteria of the Study were enrolled. Potential study subjects were thoroughly interrogated for history in local dialect along with thorough clinical examination for both Pulmonary and Extra-pulmonary tuberculosis. The patients were followed upon a weekly basis during the period of treatment. Assessment of ADRs was done by formal methods; Timing, Pattern Recognition, Background Frequency and Re-challenge and the same was recorded in ADR Reporting and Documentation Form. All the categorical data was analysed by chi-square test on 120 patients. Causality assessment of ADRs was found to be statistically significant by WHO probability scale. 46.7% of patients reported ADRs to anti-tuberculous drugs. The severity of ADR’s was graded on 3- point scale (Mild-34.2%, Moderate-9.2%, Severe-3.3%). Close clinical monitoring in all tuberculosis patients for ADRs is important. ADRs remain one of the key factors for non-compliance of treatment, a reason for multi-drug resistance tuberculosis.

Effect of combined treatment of thioperamide with some antiepileptic drugs on methionine-sulfoximine induced convulsions in mice.

Methionine-sulfoximine (MSO), a convulsant is known to increase the activity of histamine N-methyl transferase. The effect of a selective H3 receptor agonist R- ( ) methylhistamine (RAMH) and antagonist (thioperamide, THP) and some antiepileptic drugs (gabapentin and sodium valproate) have been evaluated on MSO-induced convulsions in mice. The effect of THP was also evaluated in combination with these antiepileptic drugs. Sodium valproate (300 mg/kg, po) and gabapentin (400 mg/kg, po) offered protection against MSO-induced convulsions as evidenced by a significant prolongation of latency to abnormal dorsoflexion and complete protection against mortality within 6 h of administration. THP (15 mg/kg, ip) alone and in combination with sub-effective doses of gabapentin (75 mg/kg, po) and sodium valproate (75 mg/kg, po) revealed no significant differences from the control group or either drug alone. Hence, the convulsant action of MSO does not appear to be mediated via histaminergic mechanisms.

Ethanolic Zingiber officinale R. extract pretreatment alleviates isoproterenol-induced oxidative myocardial necrosis in rats.

Ethanolic Z. officinale (ZO) extract (200 mg/kg) pretreatment for 20 days in isoproterenol (ISO)-treated rats significantly increased the levels of endogenous myocardial antioxidants (catalase, superoxide dismutase and tissue glutathione), decreased the levels of serum marker enzymes (lactate dehydrogenase, creatine kinase, aspartate transaminase and alanine transaminase) and increased myocardial lipid peroxides. Histological examination of rat's heart section confirmed myocardial injury with ISO administration and near normal pattern with ethanolic ZO extract pretreatment. The results of the present study, for the first time, provide clear evidence that the ethanolic ZO extract pretreatment enhances the antioxidant defense against ISO-induced oxidative myocardial injury in rats and exhibit cardioprotective property.

Involvement of potassium channels in hypoglycemic effect of sertraline.

Effect of 21 days administration of sertraline (30 mg/kg, po) in streptozotocin (55 mg/kg, ip) induced diabetic and non-diabetic rats produced hypoglycemia in diabetic and non-diabetic rats. Pinacidil (1mg/kg, po), when co-administered with sertraline or glimepiride antagonized the decrease in glucose levels in diabetic rats. Pinacidil (10(-6)-10(-3) M) produced dose dependent relaxation (EC50-1.58 x 10(-5) M). Neither sertraline nor glimepiride had any effect on the resting tension of ileum preparation. Both sertraline and glimepiride antagonized competitively the pinacidil-induced relaxation. The pA2 values of sertraline and glimepiride reversal of pinacidil-induced relaxation were 5.5 and 6.2 respectively. These studies suggest the involvement of K+ channels in hypoglyceimic effects of sertraline.

Investigations of anti-inflammatory activity of Jigrine.

Jigrine, a polypharmaceutical herbal formulation containing 14 medicinal plants is used in the Unani system of medicine for the treatment of liver ailments. The antiinflammatory activity of Jigrine (0.5 ml and 1.0 ml/kg, po), was evaluated against acute inflammation caused by carrageenin (injecting 0.1 ml of 1% carrageenin in 0.9% NaCl solution into plantar surface of the hind paw of the rat) and the effect of Jigrine (1 ml/kg/day, po for 7 days) was also studied on the sub-acute inflammation induced by cotton pellet granuloma. The paw volume, biochemical parameters like tissue AST, ALT, gamma-GTP and lipid peroxides and dry wt. of granuloma were measured to assess the anti-inflammatory activity. It showed a significant anti-inflammatory activity as evidenced by lowering the elevated levels of paw volume and biochemical parameters. But it could not reduce the sub-acute inflammation caused by cotton pellet granuloma. The study suggests that Jigrine has significant effect only on acute phase of inflammation caused by carrageenin. Antioxidant and membrane stabilizing action of Jigrine might be responsible for its anti-inflammatory effect.

Cardioprotective effect of cromakalim (potassium channel opener) in isoproterenol induced myocardial infarction in rats.

Animals pretreated with cromakalim (1 mg/kg,po) along with isoproterenol (85 mg/kg,sc) showed less myocardial degenerative changes on histopathological examinations when compared with those treated with isoproterenol alone. Cromakalim's beneficial effects on myocardium were in dose-dependent manner. Administration of cromakalim (po) lowered significantly the serum LDH and SGOT and depleted intracytoplasmic glycogen as demonstrated by periodic schiff staining procedure. Increase in blood clotting time was highly significant (P less than 0.001). The results suggest cardioprotective effect of cromakalim in isoproterenol induced myocardial infarction.