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Open Access
PHARMACOLOGICAL EVALUATION OF HERBAL METHIONINE IN METHIONINE DEFICIENCY AND IRON INDUCED STRESS IN BROILERS
(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2009-12) SAI GOPAL, T; USHA RANI, M(MAJOR); GOPALA REDDY, A; ANAND KUMAR, A
ABSTRACT: A total of 120 sexed male broiler chicks of Vencobb strain of day-old age were randomly divided into 8 groups consisting of fifteen chicks in each group. Group 1 was maintained on methionine deficient diet and groups 3, 5 and 7 were supplemented with herbal methionine at level 1 and 2, and synthetic methionine, respectively. Group 2 was maintained as iron added methionine deficient diet and groups 4, 6 and 8 were supplemented with herbal methionine at level 1 and 2, and synthetic methionine, respectively. All the groups were maintained on iso-nitrogenous and iso-caloric diet for a period of 6 weeks. The performance parameters were recorded at weekly intervals. Antioxidant defense profile, biomarkers of hepatic damage, renal damage, protein profile and lipid profile were carried out at 2"d, 4'h and 6th week. At 5m week phytohaemagglutinin (PHA) index and at the end of 6th week histopathological studies were carried out. The methionine deficient and iron added methionine deficient diet groups had a significant (Pe0.05) reduction in body weight, GSH, activity of SOD and catalase, and PHA index, while FCR, and the concentration of TBARS, protein carbonyls and serum creatinine, and the activity of AST were significantly (Pc0.05) increased. Supplementation with herbal methionine at level 1 and 2 respectively in groups 3 and 5 resulted in a marked improvement in all the above parameters as compared to those of methionine deficient diet. Supplementation of herbal methionine at level 2 revealed the performance comparable with synthetic methionine supplementation. Histological abnormalities were also recorded in the liver, kidney, spleen and bursa in all groups, while the groups, 5 and 7 did not reveal any abnormalities on histopathology, while the treated groups 3, 5 and 7 revealed lesions of mild intensity or signs of regeneration. Thus, it is concluded that deficiency of methionine alone, and iron also induces biological damage by means of oxidative stress and the herbal methionine in test offered better performance. The beneficial effects of herbal methionine may be attributed to its antioxidant, anti-stress, hepato-protective principles and biological utilization was as good as synthetic methionine.
Open Access
EVALUATION OF POLYHERBAL COMPOUNDS AGAINST EXPERIMENTAL OCHRATOXICOSIS IN BROILERS
(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2006) SRIKANTH, M.K; SOMASEKHAR REDDY, K(MAJOR)
ABSTRACT: The antioxidant potential of certain polyherbal compounds namely, nephtone and immuplus were assessed for prophylactic and therapeutic management of an experimental model of oxidative stress induced by ochratoxin, at a toxic level of 2.5 ppm in feed. A total of one hundred and fifty sexed male broiler chicks (Cobb strain) of day old age were procured for the study. The chicks were randomly divided into ten groups, consisting of fifteen in each group. Groups 1, 2 and 3 were maintained as basal diet control, nephtone control and immuplus control, respectively. Group 4 was maintained on ochratoxin @ 2.5 ppm in feed throughout 6 wks as toxic control without any treatment. Group 5 was maintained on ochratoxin @ 2.5 ppm in feed for the first 4 wks (28 days) of study and thereafter, maintained on basal diet for the next 2 wks (29 -42 days). Group 6 was maintained on ochratoxin @ 2.5 ppm in feed along with nephtone (@ 0.8 ml / 10 birds during first 2 wks; 1.6 ml / 10 birds during third and fourth week; 3.2 ml / 10 birds during the last 2 wks) in water, while group 7 was maintained on ochratoxin @ 2.5 ppm in feed along with immuplus (@ 50 mg / 10 birds for the first 4 wks and subsequently 100 mg / 10 birds during the last 2 wks). Groups 8, 9 and 10 were fed with ochratoxin @ 2.5 ppm in feed for the first 4 wks (28 days) of study and thereafter, group 8 was given nephtone, group 9 was kept on immuplus and group 10 on a combination of nephtone + immuplus till the termination of the experiment . Performance parameters were evaluated at weekly intervals. Antioxidant defense profile (GSH-Px, GSH-R, catalase, GSH, and TBARS), biomarkers of hepatic damage (ALT), lipid profile (total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol), protein profile (total protein, albumin, globulins and A/G ratio) and immune status (HI titre) were estimated. The activity of TBARS and HI titre were estimated once, at the end of the 6th wk, while the remaining sero-biochemical parameters were evaluated at the end of 4th and 6th wk. Histopathological studies on liver, kidney, bursa, thymus and spleen were conducted at the end of the 6th wk. Antioxidant enzyme levels and biochemical parameters were significantly altered and the histopathological studies revealed extensive degeneration, desquamation of tubular epithelium and disrupted tubular architecture with intertubular haemorrhages in the kidney sections of ochratoxin control. Degenerative changes of hepatocytes and marked central vein congestion was also noticed in the liver in the ochratoxin toxic control. These parameters were normal in the controls (groups 1, 2 and 3) and other groups that were given nephtone and immuplus either prophylactically (groups 6 and 7) or therapeutically (groups 8, 9 and 10). Thus, it is concluded that nephtone and immuplus were effective as antioxidants in preventing and countering oxidative stress by facilitating restoration of antioxidant defense mechanism. Hence, their supplementation would reduce the incidence of economic losses due to mycotoxin-induced stress.
Open Access
EVALUATION OF EFFECT OF CASSIA AURICULATA LINN SEED EXTRACT IN EXPERIMENTAL DIABETES MELLITUS IN RATS
(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2006-02) VENKATA RAO, K.V.; ADILAXMAMMA, K(MAJOR); VENKATESWARLU, U; ESWARA PRASAD, P
Open Access
SUB-ACUTE TOXICITY STUDIES ON UNPROCESSED AND PROCESSED PONGAMIA PINNATA SEED CAKE IN RATS
(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2013-02) SIRISHA, K; KALA KUMAR, B.D.P(MAJOR); GOPALA REDDY, A; MADHAVA RAO, T; ANJANEYULU, Y
ABSTRACT : The present study was aimed to evaluate the toxic and protective effects of unprocessed and processed Pongamia pinnata seed cake in rats, which were divided into 3 groups as follows: Group 1: sham control, group 2: unprocessed Pongamia pinnata seed cake included at the level of 9% in the feed (toxic control) and group 3: processed (solvent extracted-isopropyl alcohol) Pongamia pinnata seed cake (detoxified cake) included at the level of 9% in the feed. Average body weights were recorded at weekly intervals and on 28th day, organs were collected for estimation of TBARS, protein carbonyls and GSH in kidney, liver and testes homogenates and estimation of epididymal sperm count from testes collected. Sero-biochemical parameters like ALT, total proteins & globulins, total cholesterol, HDL & LDL cholesterol, creatinine and LDH were estimated at fortnight intervals. Haemotological parameters (RBC, WBC, Hb and PCV) were also estimated at fortnight intervals. Serum troponins, PHA assay and testicular LDH were estimated at the end of the experiment. Histopathology of heart, liver, kidney, spleen and testis was also studied at the end. Mean body weight gain, GSH, total proteins and globulins, PHA assay and sperm count were significantly (P < 0.05) decreased in toxic control group (group 2), while TBARS, protein carbonyls, serum LDH, intra-testicular LDH, serum ALT, creatinine, total cholesterol and serum troponins were significantly (P < 0.05) increased in group 2. There was no significant difference in TEC, TLC, Hb, PCV, HDL cholesterol, LDL cholesterol, mean body weight gain (in the 1st week) in group 2. Group 1 did not reveal any abnormalities on histopathology. Group 2 showed interfibrillar haemorrhages, congestion and edema with disruption of cardiac myofibres in heart, marked degenerative changes in tubular epithelial cells and marked dilatation of tubules in kidney, marked central vein congestion and marked bile duct hyperplasia in liver, congestion and thickening of trabecular arteries in spleen and finally marked congestion and edema with disrupted cell wall in seminiferous tubules of testes. Group 3 showed mild lesions in heart, kidney, liver, spleen and testis. From this study, it is concluded that unprocessed Pongamia pinnata seed cake induces toxicity to heart, kidney, liver, spleen and testes, and group 3 showed restoration in all the parameters studied, suggesting reduced toxic potential of processed seed cake.
Open Access
ENDOCRINE DISRUPTING ACTIONS OF CADMIUM AND EXPERIMENTAL EVALUATION OF PROTECTION BY GREEN TEA EXTRACT
(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2014-05) SHIVAKUMAR, PABBATHI; GOPALA REDDY, A(MAJOR); SRINIVASA RAO, G; ANJANEYULU, Y; RAMANA REDDY, Y; UDAYA KUMAR, M
ABSTRACT : An experimental study was conducted to evaluate the neuro-endocrine disrupting actions of cadmium and the effect of cadmium on the progeny that were born to cadmium exposed rats and to evaluate the protective role of green tea on neuro-endocrine disrupting actions of cadmium in Sprague dawley rats. Rats were randomly divided into 4 groups of 30 rats in each (male rats =12, female rats=18).Group 1 served as Sham control Group 2 treated with CdCl2, Group 3 treated with Green tea extract treatment and Group 4 Cd + green tea extract treatment. Blood was collected from all the groups at monthly intervals for analyzing sero-biochemistry (blood glucose, total cholesterol, HDL-cholesterol, triglycerides, total protein and albumin, biomarkers of cardiovascular, hepatic and renal pathology, and hormonal profile (thyroid profile, sex hormones). The key enzymes concerned with metabolism were assayed. Immune status was studied at the end of 3rd month by phytohaemagglutinin assay. Rats were subjected to neuro-behavioural studies at the end (Elevated plus maze and Morris water maze). Epididymal sperm count in males and estrous cycle pattern in females were studied. At the end of 3 months, 12 rats (6 males and 6 females) from each group were sacrificed to collect various organs and endocrine glands and subjected them to biochemical, histological and electron microscopic studies. Cadmium concentration was estimated in all the treated groups in kidney, testes, liver and brain at the end of 3 months. In all the groups, twelve (12) females were mated at the end of three months with male rats belonging to respective groups/treatments and the treatment was continued till 17th day of gestation. 50% of the pregnant rats in the respective groups were sacrificed on day 19 to study skeletal and soft tissue developmental anomalies and the rest were allowed to normal delivery. The pups of F1 generation from all the groups were kept till weaning (post-natal day 21) and were subjected to sero biochemical, neurobehavioural studies andthyroid hormone profile were estimated. There were significant alterations in sero-biochemistry biomarkers of cardiovascular, hepatic and renal pathology and hormonal profile thyroid profile, group 2 as compared to group 1.Treatment group revealed significant improvement in all the parameters as compared to group 2, while the combination treatment group 4 was found better The histological studies in group 2 revealed marked changes in all the organs studied, while groups 4 revealed moderate changes and groups 1 and 3 revealed no pathologically significant changes. The electron microscopy of kidney, testis and thyroid revealed marked alterations in architecture in group 2, while groups 4 revealed better architecture. There were no significant alteration in the TEM samples of the offspring and there were no skeletal abnormalities in the offspring as evidenced by skeletal staining. The results of the study revealed neuro-endocrine disrupting actions of cadmium and protctive role of green tea in cadmium toxicity. Further studies are warranted to know in detail on the endocrine disrupting actions of cadmium and protective role of green tea at various concentrations.
Open Access
INTERACTION STUDIES ON GYMNEMA SYLVESTRE WITH GLIMEPIRIDE AND INSULIN IN EXPERIMENTAL DIABETES MELLITUS IN RATS
(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2013-12) Srikanth, M.K; GOPALA REDDY, A(MAJOR); BHARAVI, K; MADHAVA RAO, T; KONDAL REDDY, K; ANAND KUMAR, A
ABSTRACT: An experimental study was conducted to evaluate the interaction of Gymnema sylvestre extract with insulin and glimepiride in diabetic Sprague dawley rats. Rats were randomly divided into 7 groups of 6 rats in each and blood glucose was estimated to ascertain group differences, if any. Group 1 was kept as normal control. Remaining 6 groups were induced diabetes by intraperitoneal injection of streptozotocin @ 40 mg/kg body weight. After 72 h, rats with blood glucose value of >200 mg/dl were included in the study (n=6). Treatment protocols were initiated 48 hrs post-confirmation of diabetes and continued for 2 months. Group 1: non-diabetic control, group 2: streptozotocin (40 mg/Kg i/p single dose)-induced diabetic (DM) control, group 3: Insulin treatment (4 U/kg b. wt. subcutaneously once daily), group 4: glimepiride treatment (4 mg/kg b. wt. orally once daily), group 5: Gymnema sylvestre methanolic leaf extract treatment ( 400 mg/kg b.wt. orally once daily), group 6: Insulin + Gymnema sylvestre methanolic leaf extract treatment (once daily) and group 7: glimepiride + Gymnema sylvestre methanolic leaf extract treatment (once daily). Blood glucose, body weights, sero-biochemical parameters, antioxidant profile in liver, kidney, brain and testis, ATPases, glucose 6 phosphate dehydrogenase (G6PD), cytochrome P450 (CYP450) activity and glycogen in liver, electron microscopy and histopathology of various tissues were studied at different time intervals. Also, pharmacokinetic interaction of glimepiride with Gymnema sylvestre extract was assessed. There were significant alterations in blood glucose, body weights and other biochemical parameters in diabetic control group 2 as compared to group 1. All the treated groups revealed significant improvement in all the parameters as compared to group 2, while the combination treatment in groups 6 and 7 was found better as compared to single agent-treated groups 3, 4 and 5. The histological studies revealed marked changes in group 2 in all the organs studied, while groups 3 to 5 revealed moderate changes and groups 6 and 7 revealed either minor changes or no pathologically significant changes. Group 1 was devoid of any histological alterations. The electron microscopy of kidney, pancreas and aorta revealed marked alterations in group 2, while groups 6 and 7 revealed better architecture. The pharmacokinetic study revealed the values of T1/2 (h), Ka (h-1), Ke (h-1) and Tmax (h) of glimepiride were siginificantly varied in Gymnema sylevestre pre-treated rats compared to normal rats administered with glimperide In conclusion, the study revealed that addition of Gymnema sylvestre leaf extract to insulin and glimepiride had positive pharmacodynamic interaction in improving the patho-biochemical alterations due to streptozotocin-induced diabetes mellitus in rats, which was evident from greater improvement in sero-biochemical and organ parameters in the groups that were treated using a combination of Gymnema sylvestre with either insulin or glimepiride as compared to individual agent-treated groups. Important pharmacokinetic parameters did not vary significantly when glimepiride was used in combination with Gymnema sylvestre leaf extract.
Open Access
A STUDY ON THE TERATOGENIC EFFECTS AND ORGAN TOXICITY OF NIMESULIDE AT DIFFERENT DOSE LEVELS IN PREGNANT AND PROGENY RATS
(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2011-10) SWAPNIL VIJAYKUMAR JINTPURE; USHA RANI, M(MAJOR); GOPALA REDDY, A; ANJANEYULU, Y
ABSTRACT: The present study was aimed to evaluate the teratogenic effects and organ toxicity in the dams and their progeny treated with nimesulide in gestation period at different dose levels. Seventy two female albino rats of Sprague dawley strain were divided into 3 groups and treated as follows. Group 1 served as control, group 2 received nimesulide @ 20 mg/kg body weight and group 3 received nimesulide @ 60 mg/kg body weight via intramuscular route from day 7th to 17th day of gestation. In each group, half of the pregnant rats were subjected to caessarian section on 19th day of gestation (caessarian group namely “A”) and the remaining half of the pregnant rats were allowed for normal parturition (normal parturition group namely “B”). Average body weights were recorded at weekly intervals in dams of caessarian, normal parturition group and in progeny of normal parturition group up to weaning day. On 19th day, half of pregnant dams in each groups were subjected to caessarian for uterine weights with progeny, resorption sites, inborn progeny body weight, litter size, live and dead numbers, male: female progeny numbers, skeletal staining of progeny with Alizarin-Red S, Alcian blue-Alizarin Red S stains and soft tissue developmental anomalies. The remaining half, allowed for normal parturition and recorded inborn progeny body weights, litter size, live-dead numbers, male: female progeny numbers and other abnormalities, if any. Serum biochemical profiles (Albumin, ALP, ALT, AST, BUN, creatinine, GGT and total protein) were recorded on 19th day of gestation in dams of caessarian group and the same serum biochemical profiles and haematology (RBC, WBC and haemoglobin) was recorded on post natal day 21 in progeny of normal parturition group. TBARS and GSH were estimated on 19th day in liver and kidney homogenates. Histopathology of kidney, liver, stomach and ovary were studied in dams of caessarian group on 19th day and liver, kidney and heart in progeny of normal parturition group on weaning day. The study showed no evidence of teratogenicity by skeletal staining, uterine weights with progeny, resorption sites, litter size, inborn progeny body weights, male: female progeny numbers, live and dead numbers, and weekly body weights in progeny upto weaning. There was a significant difference in serum biochemical profiles of dams and was more evident in nimesulide treated at 60 mg/kg body weight. Further, there was no significant difference in the haematological parameters and serum biochemical profiles of progeny except an increase in BUN and creatinine, which was more evident in group 3 as compared to groups 2 and 1. Treatment with nimesulide at higher dose induced oxidative stress and tissue damage of liver and kidney as evident from increased levels of MDA and decreased levels of GSH, histopathology of liver, kidney and stomach of dams and kidney of progeny of normal parturition group. It is concluded that nimesulide at 60 mg/kg body weight in pregnant dams showed more significant damage to liver and kidney as from light microscopic findings of liver, kidney, stomach and ovary as compared to the dose of 20 mg/kg body weight and control.
Open Access
TOXICODYNAMIC INTERACTION OF LEAD WITH CADMIUM AND THERAPEUTIC EVALUATION OF N-ACETYL L-CYSTEINE IN RATS
(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2011-07) ANlL KUMAR, B; GOPALA REDDY, A(MAJOR); RAVl KUMAR, P; MADHAVA RAO, T; ANAND KUMAR, A
ABSTRACT: An experimental study was conducted to evaluate the molecular mechanisms of lead and cadmium toxicity and their toxicodynamic interaction, and to evaluate therapeutic potential of N-Acetyl L-cysteine (NAC) against the toxicity in Wstar rats. After an acclimatization period of 2 weeks, rats were randomly divided into 8 groups comprising of 6 rats in each. Group 1 was kept as normal control throughout the experimental period, 2 was given NAC @ 300 mg per kg body weight administered by oral gavage, 3 was given lead (lead acetate @ I000 ppm in feed), 4 was given cadmium (cadmium chloride @ 300 ppm in feed), 5 was given lead + cadmium as per above doses in feed, 6 was given lead + NAC as per above schedule, 7 was given cadmium + NAC as per above schedule, and group 8 was given lead + cadmium + NAC as per above schedule for 3 months. Body weights, haematology (TEC, TLC, Hb, PCV, MCH and MCHC), activity of 6-ALAD and erythrocytic SOD, sero-biochemical parameters (ALT, CPK, troponins, plasma TBARS and serum creatinine), antioxidant profile (GSH, GST, TBARS and protein carbonyls) in liver, kidney, heart, testis and brain, ATPases and tissue lipids in liver and brain, neurotransmitters (Ach and glutamate) in brain, CYP450, glycogen and G6PD in liver, weight of testes, testicular LDH and sperm count, electron microscopy of kidney in cadmium exposed groups and histopathology of liver, kidney, testis and heart were studied. Also, interaction of lead and cadmium with zinc and copper in liver, kidney, heart, testis and brain was assessed. The present study revealed significant alterations in body weights, haematology, sero-biochemical parameters, antioxidant profile, ATPases, tissue lipid profile, neurotransmitter, CYPd50, glycogen, GGPD, weights of testes, testicular LDH, sperm count, and concentration of zinc and copper in toxic control groups 3, 4 and 5 as compared to control and NAC-treated groups. The toxic combination (Pb + Cd) group 5 showed significant alterations in most of the parameters studied as compared to Pb alone and Cd alone administered groups. All the NAC-treated groups revealed significant improvement in all the parameters. The histological studies of liver, kidney, testis and brain revealed marked changes in toxic control groups, while therapeutic groups revealed mild changes or no pathologically significant changes. Groups 1 and 2 were devoid of any alterations. The electron microscopy of kidney revealed marked alterations in kidney architecture in groups 4 and 5, while groups 7 and 8 revealed better architecture. The results of the investigation revealed that lead, cadmium' and their combination induced toxicity to the biological system due to the excess generation of free radicals and impairment of antioxidant defenses. Toxic effects were more pronounced in the group that received a combination of lead and cadmium suggesting positive toxicodynamic interaction. Use of NAC countered the adverse effects of lead and cadmium induced toxicity to a major extent suggesting its antioxidant potential owing to replenishment of tissue pool of GSH. Further, NAC administration reduced the extent of accumulation of lead and cadmium in various tissues.
Open Access
INTERACTION OF TRIGONELLA FOENUM GRAECUM WITH INSULIN AND GLIMEPIRIDE IN EXPERIMENTAL DIABETES MELLITUS IN RATS
(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2011-01) HARITHA, C; GOPALA REDDY, A(MAJOR); SRINIVASA RAO, G; ANJANEYULU, Y; MADHAVA RAO, T; RAMANA REDDY, Y
ABSTRACT: An experimental study was conducted to evaluate the interaction of fenugreek seed powder with insulin and glimepiride in diabetic Sprague dawley rats. Rats were randomly divided into 7 groups of 8 rats in each and blood glucose was estimated to ascertain group differences, if any. Group 1 was kept as normal control. Remaining 6 groups were induced diabetes by intraperitoneal injection of streptozotocin @ 40 mg/kg body weight. After 72 h, rats with blood glucose value of >250 mg/dl were included in the study (n=8). Treatment protocols were initiated from day 2 post-confirmation of diabetes and continued for 8 wks. Group 1: non-diabetic control, group 2: streptozotocin (40 mg/Kg i/p single dose)-induced diabetic (DM) control, group 3: Insulin treatment (4 U/kg once daily), group 4: glimepiride treatment (4 mg/kg orally once daily), group 5: fenugreek seed powder treatment (1 g/kg orally once daily), group 6: Insulin + fenugreek seed powder treatment (once daily) and group 7: glimepiride + fenugreek seed powder treatment (once daily). Blood glucose, body weights, sero-biochemical parameters, antioxidant profile in liver, kidney, brain and testis, ATPases in liver and brain, relative weights of kidney and testes, electron microscopy of kidney and histopathology of various tissues were studied at different time intervals. Also, pharmacokinetic interaction of glimepiride with fenugreek seed powder was assessed. There were significant alterations in blood glucose, body weights and other biochemical parameters in diabetic control group 2 as compared to group 1. All the treated groups revealed significant improvement in all the parameters as compared to group 2, while the combination treatment groups 6 and 7 were found better as compared to single agent-treated groups 3 through 5. The histological studies revealed marked changes in all the organs studied, while groups 3 to 5 revealed moderate changes and groups 6 and 7 revealed either minor changes or no pathologically significant changes. Group 1 was devoid of any alterations. The electron microscopy of kidney revealed marked alterations in kidney architecture in group 2, while groups 6 and 7 revealed better architecture. Fenugreek seed powder treatment increased AUC and elimination half life of glimepiride in combination as compared to glimepiride-alone treated group, while the Cmax and tmax did not vary between groups 4 and 7. The results of the study revealed positive pharmacodynamic interaction between fenugreek and either insulin or glimepiride in improving the patho-biochemical alterations in diabetic rats. Further, there was a favourable pharmacokinetic interaction. Further studies are warranted to estimate P-gp and OATP activities along with CYP2C9 estimation for better understanding of pharmacokinetic interactions of fenugreek and glimepiride in diabetes mellitus.

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