Enzymes In Female Rats Research Articles

Toxicological impact of technical imidacloprid on ovarian morphology, hormones and antioxidant enzymes in female rats

Technical imidacloprid was evaluated for its effect on ovarian morphology, hormones and antioxidant enzymes in female rats after 90days oral exposure. Luteinizing hormone (LH), follicle stimulating hormone (FSH) and progesterone levels were estimated in serum of rats and activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and level of reduced glutathione (GSH) and lipid peroxidation (LPO) were estimated in ovary after oral administration of imidacloprid (5, 10, and 20mg/kg/day) for 90days. Decreased ovarian weight together with significant patho-morphological changes in follicles, antral follicles and atretic follicles were observed at 20mg/kg/day. Imidacloprid at 5 and 10mg/kg/day has not produced any significant changes in ovarian morphology, hormones and antioxidant status of ovary. However 20mg/kg/day dose has produced significant alterations in the levels of LH, FSH and progesterone. Similarly significant changes in SOD, CAT, GPx, GSH, and LPO were observed at 20mg/kg/day dose level. Therefore, it is concluded that imidacloprid at 20mg/kg/day dose level has produced significant toxicological impact on ovary of female rats as evident by pathomorphological changes, hormonal imbalance and generating oxidative stress and can be considered primarily as Lowest Observed Effect Level (LOEL) for chronic study.

Chokeberry ( Aronia melanocarpa) juice modulates 7,12-dimethylbenz[a]anthracene induced hepatic but not mammary gland phase I and II enzymes in female rats

Chokeberry is a rich source of procyanidins known to have several types of biological activity including anticarcinogenic potential in experimental models. In this study we examined the effect of chokeberry juice on the hepatic and mammary gland carcinogen metabolizing enzyme expression altered by the polycyclic aromatic hydrocarbon, 7,12-dimethylbenz[a]anthracene (DMBA). Sprague–Dawley rats were gavaged with chokeberry juice (8 ml/kg b.w.) for 28 consecutive days. DMBA was administered i.p. on the 27th and the 28th days. Pretreatment with chokeberry juice reduced the activity of CYP1A1 and increased that of CYP2B involved in metabolic activation/detoxication of DMBA in rat liver, as well as expression and activity of phase II enzymes. Chokeberry juice had no effect on these parameters in the mammary gland and DMBA induced DNA damage in rat blood cells. These results together with our earlier observations indicate that metabolic alterations induced by chokeberry feeding are tissue specific and depend on the class of carcinogen.

Effect of Pineal Proteins at Different Dose Level on Fluoride-Induced Changes in Plasma Biochemicals and Blood Antioxidants Enzymes in Rats

Pineal glands secrets melatonin and various proteins and peptides which has many physiological functions. In keeping with this view, present experiment was conducted to know the effect of buffalo (Bubalus bubalis) pineal proteins (PP) at different dose level on fluoride-induced changes in plasma biochemicals and blood antioxidants enzymes in female rats. For this, we took 30 adult female Wistar rats (133-145g body weights, BW) and divided into five groups (control, group I; 150ppm fluoride (F), group II; F+ 50µg pineal proteins, group III; F+ 100µg PP, group IV; F+ 200µg PP, group V). We administered fluoride (150ppm, drinking water) and F+ pineal proteins at 50, 100, and 200µg/kg BW, i.p. daily for 21days. Blood samples were collected at the end of the experiments to estimate plasma glucose, proteins, F, lipid peroxidation (LPO), alkaline phosphatase (ALP), and acetyl cholinesterase (AChE) activity. Red blood cells (RBCs) were separated for analysis of LPO, AChE, catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx), and glutathione reductase (GR) in different groups of animals. Total plasma glucose and protein level did not significantly change in F-treated rats. Plasma ALP and F level were significantly (p < 0.05) high in group II as compared with control and groups III, IV, and V. Administration of PP at different dose level significantly (p < 0.05) reduced the F concentration and ALP activity. Plasma and RBCs AChE activity was significantly (p < 0.05) reduced in F-treated animals as compared with control rats and significantly (p < 0.05) elevated on exogenous administration of PP (groups III and IV). Plasma and RBCs LPO level was significantly (p < 0.05) high in F-alone-treated rats, and PP caused significant (p < 0.05) reduction of LPO in groups IV and V. However, PP treatment in group IV brought better amelioration of F-induced high LPO than in groups III and V. At no dose level, PP-ameliorated F-induced depression of RBCs GSH, CAT, GR, and GPx level. Interestingly, SOD activity was elevated in dose-dependent manner at different dose level of PP in groups III, IV, and V than control and F-administered rats. These findings clearly indicate the beneficial effects of buffalo pineal proteins on fluoride-induced adverse changes in certain plasma biochemical and blood antioxidant systems of rats. It further indicates that PP has dose-dependent ameliorative function against F-induced adverse effects in plasma and blood.

Effects of bile duct ligation on hepatic expression of female-specific CYP2C12 in male and female rats.

Gender differences in hepatic sex steroid and drug metabolism result from hormonal regulation of specific cytochrome P450 genes (CYP). In male rats, bile duct ligation (BDL) is associated with down-regulation of the male-specific genes, CYP2C11 and CYP3A2, together with a decrease in serum testosterone levels and a two- to three-fold increase in serum estradiol concentrations. We anticipated that if estrogen is responsible for down-regulation of male-specific CYPs in BDL male rats, the female-specific CYP2C12, which is not normally present in adult male rat liver, should be up-regulated. We examined this proposal by determining the profile of hepatic cytochrome P450 enzymes in female rats subjected to BDL, and by seeking evidence for expression of CYP2C12 in male rats that do not normally express this gene. In female rats killed 5 days after BDL, total cytochrome P450 content and NADPH-cytochrome P450-reductase (P450-reductase) were decreased to 74% and 58% of control, respectively. Microsomal enzyme activities attributable to CYP2A1, CYP2C6, and CYP2E1 were 50% to 60% of control, but ethylmorphine N-demethylase, which in female liver is catalyzed by CYP2C12 and to a lesser extent CYP2C6, was significantly less affected (81% of control). Likewise, levels of CYP2C6 and P450-reductase proteins were decreased in proportion to the corresponding enzyme activities (50% to 60%), while CYP2C12 protein (and mRNA levels) were not altered in BDL female rat liver. In sham-operated male rats, transcripts for CYP2C12 were rarely detected, but mRNA levels rose to appreciable levels within 24 hours of BDL, and CYP2C12 protein was expressed in hepatic microsomes of BDL male rats. Administration of estradiol to male rats produced a similar elevation of CYP2C12 mRNA, to values approximately 40% of female rats. It is concluded that CYP2C12 is up-regulated in male rats with cholestasis caused by BDL, while CYP2C12 protein is preserved in female rats when other microsomal proteins are decreased. These changes may be related to the increase in serum estradiol levels that result from altered hepatic steroid metabolism. The results demonstrate that activities of individual drug-metabolizing enzymes in liver disease can be determined by dysregulation of the constitutive expression of hepatic CYP genes.

Diabetes-induced Metabolic Alterations in Heme Synthesis and Degradation and Various Heme-containing Enzymes in Female Rats

Diabetes-induced alterations in heme and hemoproteins, as well as its relationship to drug-mediated induction of ALA Synthase (ALA-S), were examined in female Sprague-Dawley rats. Animals were rendered diabetic by a single i.v. injection of streptozotocin (STZ, 65 mg/kg) and measurements were made at various times after treatment. The basal levels of the key enzymes involved in heme synthesis, ALA-S and ALA-dehydratase (ALA-D), were decreased about 36% and 54%, respectively, 44-46 days after diabetes induction. Furthermore, the catabolism of heme that occurs via microsomal heme oxygenase progressively decreases in activity during the course of diabetes, and reaches 69% of control in 90-day diabetic animals. The basal levels of heme, cytochromes P-450 and b5 were elevated about twofold in diabetic rats as compared with their corresponding control values. The activity of benzo(a)pyrene hydroxylase in diabetic rats was also increased in proportion to the microsomal content of cytochrome P-450. In contrast, delta 4-hydrogenase, the rate-limiting enzyme in corticosterone metabolism, exhibited a 35-65% decrease in activity throughout the experimental period. Tryptophan pyrrolase activity (total, holo-, and apoenzyme) was elevated about 2.5-fold in STZ diabetic rats. In vivo insulin therapy of diabetic animals antagonized the effect of the diabetic state on the above measured parameters. Treatment with aminoglutethimide resulted in about a twofold elevation in ALA-S activity in control as well as chronically diabetic rats. However, a similar stimulatory response in ALA-S activity to CoCl2 administration was observed only in control or insulin-treated diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes-induced metabolic alterations in heme synthesis and degradation and various heme-containing enzymes in female rats

Diabetes-induced metabolic alterations in heme synthesis and degradation and various heme-containing enzymes in female rats

Effect of cadmium on hepatic and renal gluconeogenic enzymes in female rats

Earlier, we have reported that cadmium (Cd) induced gluconeogenesis in male rats. Since females are as much exposed to cadmium as are males, this study was conducted to determine Cd effects on gluconeogenesis in female rats. Adult female rats were injected intraperitoneally (i.p.) with Cd at dose levels of 0.25, 0.75 and 1.25 mg kg body weight per day for 4 weeks. The controls received saline for the same length of time. Daily food consumption and body weight gain were recorded. At the end of 2 and 4 weeks, 4 rats from each group were killed. Extension of treatment with 1.25 mg Cd for 4 weeks resulted in extreme Cd toxicity killing all animals before the completion of full treatment period. There were no significant changes in total body weight gain and weights of liver and kidney due to Cd. Serum protein increased significantly in animals receiving 0.75 and 1.25 mg Cd for 4 and 2 weeks, whereas serum glucose increased only in animals injected with 1.25 mg Cd for 2 weeks. SGOT and SGPT were elevated ( P < 0.01) in dose- and time-dependent fashion. Activities of three key gluconeogenic enzymes glucose-6-phosphatase (G-6-Pase), fructose-1,6-diphosphatase (FD-Pase), and phosphoenolpyruvate carboxykinase (PEPCK) in liver and kidney were induced significantly ( P < 0.01) in animals injected with 0.75 mg for 2 and 4 weeks and 1.25 mg for 2 weeks, and these increases were dose- and time-related. These results suggest that Cd alters hepatic and renal gluconeogenesis in female rats also.

Effect of aflatoxin B1 on hepatic drug-metabolizing enzymes in female rats. Interaction with a contraceptive agent.

1. The effect of a contraceptive on aflatoxin B1 toxicity has been studied in female rats treated for 15 consecutive days with repeated doses of aflatoxin (0.40 mg/kg/day), norethindrone (0.60 mg/kg/day) and ethynylestradiol (0.012 mg/kg/day). 2. Increases occurred in hepatic microsomal cytochrome P-450 content (31%), and in the activities of epoxide hydrase (77%), UDP-glucuronyltransferase (67%) and gamma-glutamyltransferase (78%). 3. Aflatoxin alone caused a 22% increase in GSH S-epoxide transferase activity, whereas the contraceptive given alone or combined with aflatoxin increased the hepatic reduced glutathione. 4. The effect of aflatoxin plus contraceptive was not additive. 5. The effects caused by aflatoxin and the contraceptive were similar, and the contraceptive (depending on its progestogen/estrogen ratio), may modify aflatoxin toxicity by increasing the drug-metabolizing enzyme activities and the concentration of hepatic glutathione.