PRE-084 ameliorates adenine-induced renal fibrosis in rats.

2-(4-morpholinoethyl)- 1-phenylcyclohexane-1-carboxylate hydrochloride (PRE-084) is a selective sigma 1 receptor agonist. It has been shown that PRE-084 protected various tissues from experimental injury. However, no reports are available on its effect on renal fibrosis. Rat model of adenine-induced chronic kidney disease was chosen to study this. Adenine feeding in rats caused renal dysfunction as shown by increased serum creatinine and reduced creatinine clearance along with increased high molecular weight (HMW) urine protein excretion. Further, adenine feeding induced profibrotic changes in the kidney as reflected by increased expression of alpha-smooth muscle actin (α-SMA), fibroblast specific protein-1 (FSP-1) and matrix metalloproteinase-2 (MMP-2) activity; reduced cytokeratin expression. Further, there was excess deposition of extracellular matrix in the kidney, a striking character of fibrosis. However, administration of PRE-084 to adenine fed rats led to reduction in creatinine and proteinuria parameters partly. This was accompanied by reduced expression of α-SMA, FSP-1 and MMP-2 activity and slight restoration of cytokeratin levels leading to reduced extracellular matrix deposition in the kidney. These data demonstrate that PRE-084 partly ameliorated renal dysfunction and exhibited anti-fibrotic potential in the kidney of adenine fed rats.

Soft Tissue Foreign Body: Utility of High Resolution Ultrasonography.

INTRODUCTION: Minor percentage of wooden foreign bodies is radio-opaque. High Resolution Ultrasonography (HRUSG) though existing is sparsely used as a primary imaging modality for diagnosis and localization of retained foreign body. AIM: To evaluate the diagnostic accuracy of High Resolution Ultrasonography (HRUSG) in diagnoses and localization of retained foreign body. MATERIALS AND METHODS: A prospective study with registered 46 patients with history of foreign body injury which were initially imaged with conventional radiography was enrolled. Later patients were subjected for high resolution USG of the diseased part with a linear transducer. Surface marking was done for all subjects to assist the surgical exploration. Ultrasound findings were correlated with surgical exploration and histopathological findings. RESULTS: Out of 46 patients, forty one showed foreign body with foreign body inflammatory reaction in the form of abscess and/or granulation tissue on high resolution ultrasonography. No foreign body was detected in five patients but they showed focal hypoechogenicity which represented abscess and/or haematoma. On surgical exploration, two out of 41 patients did not reveal foreign body where as rest were found to have foreign body with foreign body inflammatory reaction. Sensitivity and negative predictive value of the current study is 100%. CONCLUSION: High resolution USG is not only an efficient modality in diagnosing and localizing the foreign body in soft tissue, but can also be utilized for guiding the foreign body removal.

Pharmacodynamic interaction of fenugreek, insulin and glimepiride on sero-biochemical parameters in diabetic Sprague-Dawley rats.

AIM: This study was undertaken to assess the pharmacodynamic interaction of fenugreek, insulin and glimepiride on sero-biochemical parameters in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: A total of 56 male Sprague-Dawley rats, randomly divided into seven Groups. Group 1: Non-diabetic control; Group 2: Streptozotocin induced diabetic control; Groups 3, 4 and 5 were treated with insulin, glimepiride and fenugreek seed powder, respectively; Groups 6 and 7: Insulin + fenugreek seed powder treatment and glimepiride + fenugreek seed powder treatment respectively, in diabetic rats. Body weights, blood glucose, lipids total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG) and proteins (total protein, albumin, globulin, A/G ratios) were studied at different time intervals. Rats were sacrified at the end of 8 weeks, pancreas and aorta collected for histopathological study. RESULTS: The results of Group 2 showed significantly (p<0.05) higher concentration of glucose, TC, TG, LDL, globulin, A/G ratios and significantly (p<0.05) lower concentration of albumin, total protein, HDL and body weights when compared to Group 1 at the end of 4(th) and 8(th) weeks intervals with marked alteration in histopathology of pancreas and aorta. All the treatment Groups 3-7 showed significantly (p<0.05) improvement in the all the parameters and the Groups 6 and 7 showed highest decrease in the concentration blood glucose, TC, TG, LDL and increase in the albumin, total protein and body weights during 6(th) and 8(th) week, respectively. CONCLUSION: The treatment with fenugreek, insulin and glimepiride countered the alteration in the sero biochemical parameters in diabetic rats, and their combination was found a positive interaction in improving the sero biochemical status of diabetic rats.

Evaluation of protective action of fenugreek, insulin and glimepiride and their combination in diabetic Sprague Dawley rats.

The present study was conducted to assess the effect of fenugreek, insulin and glimepiride alone and their combination in diabetic rat liver. Fifty six male Sprague dawley rats of uniform age were randomly divided into seven groups. Group 1: Non-diabetic control; Group 2: Streptozotocin (40 mg/Kg i/p single dose)-induced diabetic control; Group 3: Insulin (4 U/kg once daily for 8 weeks) treatment in diabetic rats; Group 4: Glimepiride (4 mg/Kg orally once daily for 8 weeks) treatment in diabetic rats; Group 5: Fenugreek seed powder treatment (1 g/kg orally once daily for 8 weeks) in diabetic rats; Group 6: Insulin + Fenugreek seed powder treatment (once daily for 8 weeks) in diabetic rats; Group 7: Glimepiride + Fenugreek seed powder treatment (once daily for 8 weeks) in diabetic rats. Livers were collected at the end of experiment for histopathology and estimation of reduced glutathione (GSH), thiobarbituric acid reacting substances (TBARS), protein carbonyls, glutathione S-transferase (GST), glucose-6-phosphate dehydrogenase (G6PD), Na(+)/K(+) ATPase and Mg(2)+ ATPase, cytochrome P450 (CYP) and glycogen. There was an increase in the concentration of TBARS and protein carbonyls, and decrease in the concentration of GSH and glycogen, and the activity of GST, G6PD, Na(+)/K(+) ATPase and Mg(2)+ ATPase in diabetic livers, while treatment groups showed significant (P < 0.05) increase in the above parameters. The histology of liver revealed marked changes in diabetic rats and mild changes in combination treatment groups. The treatment with fenugreek, insulin and glimepiride improved the liver parameters in diabetic rats and their combination showed a beneficial effect on liver.

Evaluation of Herbal Neonatal Chick Care Against Iron-induced Toxicity in Broilers.

A study was conducted to evaluate the protective effect of herbal Neonatal Chick care (NNCC) against iron-induced oxidative stress. A total of 130 day-old sexed male broiler chicks (Vencobb strain) were randomly divided into six groups consisting of 25 chicks each in groups 1-4 and 15 each in groups 5 and 6. Group 1 was maintained on basal diet, groups 2 and 3 on herbal NNCC at 6 and 8 g/chick/day, respectively, for 2 days immediately after hatching and later continued with basal diet up to 6 wk. Group 4 was given FeSO(4) at 0.5% of feed for 6 wk, while groups 5 and 6 were given NNCC as in groups 2 and 3, and later continued with the FeSO(4) as in group 4 for 6 wk. The concentration of thiobarbituric acid reactive substances (TBARS), protein carbonyls, glucose and calcium, and the activity of alanine transaminase (ALT) were significantly (P<0.05) increased in group 4 at the end of 6(th) week, while the concentration of reduced glutathione (GSH), and the activities of superoxide dismutase (SOD) and catalase, phytohemagglutinin (PHA) index and HI titer were significantly (P<0.05) decreased in group 4. The NNCC treated groups (2, 3, 5 and 6) showed marked improvement in all the above parameters. It can be concluded that herbal NNCC offered protection and proved beneficial in resisting the adverse effects of stressor.

Evaluation of Iron-induced Oxidative Stress and its Amelioration by Certain Herbs in Broilers.

A total of 225 male broiler chicks (Cobb strain) of day-old age were randomly divided into 15 groups consisting of 15 chicks in each group. Group 1 was maintained as basal diet control and group 2 on ferrous sulfate at 0.5% in feed throughout 6 wk as iron toxic control without any treatment. Groups 3-15 were maintained on FeSO(4) at 0.5% in feed for the 4 wk (28 days) of study and thereafter administered with different herbs and their combinations for the remaining 2 wk. The blood samples were drawn from wing vein at the end of 4(th) and 6(th) weeks from the birds in each group for the assay of superoxide dismutase (SOD) and catalase. Sera samples were separated from the blood for the estimation of alanine transaminase (ALT) and serum creatinine. The birds were sacrificed at the end of 6(th) wk and tissues were collected for the assay of reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) in liver and kidney homogenates. The activities of SOD, catalase and ALT, and the concentration of TBARS and serum creatinine were increased significantly (P<0.05), while the concentration of tissue GSH was decreased significantly (P<0.05) in all the groups as compared to basal diet control and the values showed significant improvement in groups 3-15 that were treated during the last 2 weeks. It is concluded that iron induces toxicity by generating reactive oxygen species, and antioxidant herbs are useful in treating the iron-induced toxicity.

Hepatotoxicity studies in the progeny of pregnant dams treated with methimazole, monocrotophos and lead acetate.

An experimental study was conducted to evaluate the hepatotoxic effects in the progeny of dams treated with methimazole, monocrotophos (MCP) and lead acetate. Female pregnant albino rats of Wistar kyoto strain were divided into five groups and treated as follows, from day 3 of pregnancy till weaning of pups on postnatal day (PND) 21. Group 1 served as sham control, group 2 received methimazole 0.02% in drinking water, group 3 received MCP (0.3 mg/kg orally), group 4 received lead acetate at 0.2% in drinking water and group 5 received MCP + lead acetate. Thyroid hormone profile was recorded on 14 (th)day of gestation in dams. Eight pups from each group were euthanized on PND 21 and 90, and liver tissues were collected for analysis. Thiobarbituric acid reactive substances (TBARS), protein carbonyls and reduced glutathione (GSH) of liver were studied on PND 21 and 90, while the activities of Na (+)/K(+)ATPase and Mg (2+)ATPase in the liver were studied on PND 90. T(3), T(4), GSH, Na(+)/K(+)ATPase and Mg(2+)ATPase were significantly (P<0.05) decreased, while TBARS and protein carbonyls were significantly (P < 0.05) increased in all the test groups as compared to group 1. From this study, it is concluded that both MCP and lead acetate have a possible influence on thyroid gland of dams as the thyroid profile was altered significantly and the hepatotoxic effects were comparable to those induced by methimazole.

Interaction study on garlic and atorvastatin with reference to nephrotoxicity in dyslipidaemic rats.

A total of 56 male Sprague dawley rats of uniform weight and age were randomly divided into seven groups consisting of eight rats in each group. Groups 1, 2, and 3 served as plain control, dyslipidaemic control (DL), and atorvastatin control, respectively. Groups 4, 5, 6, and 7 received 1, 0.5, 0.25, and 0.75% fresh garlic w/w in feed, respectively in addition to the high-fat and high-cholesterol diet and administered with atorvastatin orally for 12 weeks at the rate of 10, 5, 7.5, and 2.5 mg/kg b.wt., respectively. Plasma creatinine was estimated at 4-week intervals, whereas histopathology, electron microscopy, and estimation of TBARS concentration in kidney were conducted at the end of experiment. The TBARS concentration in DL was significantly (P<0.05) increased when compared with groups 1, 3, 6, and 7. On histopathological examination, kidney sections of group 3 had mild degenerative changes in the tubules with fatty change in few tubules, while groups 4 and 5 exhibited mild-to-moderate degenerative and fatty changes in tubules with inter tubular hemorrhages. The electron microscopy of group 2 showed hypertrophy of Bowman's capsule, while that of group 4 showed secretary deposits in the cytoplasm. The interaction studies on kidney indicated that high dose of atorvastatin + garlic has negative safety profile when compared with groups having low dose of statin and high dose of garlic.

Oxidative Stress Induced by Diclofenac Alone and under the Influence of Certain Variables in Broilers.

Diclofenac toxicity was studied in male broiler chicks (Cobb strain) of a day old age. The chicks were randomly divided into eight groups consisting of 10 in each group. Group 1 was kept as basal diet control (1-32 days), group 2 on basal diet for 32 days + diclofenac (0.8 mg/kg body weight I/M) on day 24, 26, 28, 30, and 32, group 3 on basal diet for 32 days + cyclophosphamide (50 mg/kg body weight I/M once daily) from day 20 to 23, group 4 on high-protein, high-calcium, low vitamin A (HPHC) diet (1-32 days), group 5 on basal diet + diclofenac + cyclophosphamide (as per the schedule), group 6 on HPHC + diclofenac (as per the schedule), group 7 on HPHC + cyclophosphamide (as per the schedule), and group 8 on HPHC + diclofenac + cyclophosphamide (as per the schedule). The activity of TBARS, SOD, and catalase revealed a significant (P< 0.05) increase, while there was a significant (P < 0.05) decrease in the concentration of GSH in liver in the groups given diclofenac either alone or in combination with other variables. There was no significant difference in the diclofenac residue levels. The electron microscopy of liver revealed lesions of mild to marked severity in different combinations. It can be concluded that diclofenac has the toxic potential in poultry at subtherapeutic doses and further the toxic effects were more pronounced under the influence of immunosuppressants and HPHC diet.