Alterations of lipid profile in plasma and liver of diabetic rats: effect of hypoglycemic herbs

The effect of three species of hypoglycemic herbs (Termis, Halfa barr, or Kammun Quaramany) on the lipid profile was investigated in plasma and liver tissues of diabetic and herbs-treated diabetic rats. This profile includes total lipids (TL), triglycerides (TG), cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL). A dose of 1.5 ml of aqueous suspension of each herb/100 g body weight (equivalent to 75 mg/100 g body weight) was orally administered daily to alloxan-diabetic rats for four weeks. The present study showed 2-fold increase (p<0.05) in the plasma glucose level of diabetic rats, which received alloxan as a single dose of 120 mg/kg body weight, relative to the mean value of control group. This elevated glucose level was restored to its normal level after treatment with any one of the three herbs. Furthermore, the levels of TL, TG, cholesterol, LDL and VLDL were significantly (p<0.05) increased in the plasma and the liver tissues of diabetic rats compared to the control group, whereas HDL level was significantly (p<0.05) decreased. The plasma levels of all above parameters were normalized after treatment of the diabetic rats with Kammun Quaramany. Treatment of diabetic rats with Tennis normalized TG, cholesterol, LDL and VLDL levels, but Halfa barr restored the induced levels of plasma cholesterol, LDL and HDL to their normal levels. On the other hand, treatment with any of the three herbal suspensions could not restore the concentrations of the all tested parameters in the liver. These data demonstrated that the glycemic control of any of the three herbal suspensions was associated with their hypocholesterolemic effects on the hypercholesterolemia of the alloxan-induced diabetic rats. Moreover, the Kammun Quaramany showed the most potent effect.     

Effects of benzo[a]pyrene as an environmental pollutant and two natural antioxidants on biomarkers of reproductive dysfunction in male rats

Benzo[a]pyrene (B[a]P) is an environmental toxicant and endocrine disruptor. Therefore, the aim of the present study was to investigate the toxicity of B[a]P in testis of rats and also to study the role of silymarin and thymoquinone (TQ) as natural antioxidants in the alleviation of such toxicity. Data of the present study showed that levels of testosterone, estrogen and progesterone were significantly decreased after treatment of rats with B[a]P. In addition, B[a]P caused downregulation of the expressions of steroidogenic enzymes including CYP17A1 and CP19A1, and decreased the activity of 17-β hydroxysteroid dehydrogenase (17β-HSD). Moreover, B[a]P decreased the activities of antioxidant enzymes including catalase (CAT), glutathione peroxidase (GP_X) and superoxide dismutase (SOD), and significantly increased free radicals levels in testis of male rats. However, pretreatment of rats with silymarin prior to administration of B[a]P was found to restore the level of free radicals, antioxidant status, and activities of steroidogenic enzymes to their normal levels in testicular tissues. Moreover, histopathological finding showed that silymarin recovered the abnormalities occurred in tubules caused by B[a] P in testis of rats. On the other hand, TQ showed pro-oxidant effects and did not ameliorate the toxic effects of B[a] P on the testicular tissue since it decreased antioxidant enzymes activities and inhibited the protein expression of CYP11A1 and CYP21A2 compared to control rats. Moreover, TQ decreased the levels of testosterone, estrogen, and progesterone either in the presence or absence of B[a]P. It is concluded that B[a]P decreased testosterone levels, inhibited antioxidant enzymes activities, caused downregulation of CYP isozymes involved in steroidogenesis, and increased free radical levels in testis. Moreover, silymarin was more effective than TQ in restoring organism health and alleviating the deleterious effects caused by B[a]P in the testis of rats. Due to its negative impact, it is highly recommended to limit the use of TQ as a dietary supplement since millions of people in the Middle East are using it to improve their health.

     

Carcinogen-metabolizing enzymes and insecticides

The present study was under taken to demonstrate the effect of some commonly used insecticides on the activity of cytochrome P450 system including cytochrome b5, aryl hydrocarbon [benzo(a)pyrene] hydroxylase (AHH), N-nirosodimethylamine N-demethylase I [NDMA-dI] and NADPH-cytochrome c reductase as phase I of drug oxidation. In addition, the activity of glutathione S-transferase (GST), glutathione reductase (GR), and the level of glutathione (GSH) were determined in the liver of male mice after oral administration of sumithion, dursban, chlordane, methoxychlor, heptachlor epoxide, and lindane as single (24h) or as repeated doses for six consecutive days. Oral administration of sumithion, dursban, chlordane, methoxychlore, and heptachlor epoxide as repeated doses decreased: (i) the hepatic content of cytochrome P450 by 36, 37, 47, 37, and 67%, respectively, (ii) AHH activity by 28, 29, 70, 31, and 79%, respectively, (iii) NDMA-dI activity by 43, 44, 32, 27, and 31, respectively. On the other hand, sumithion, chlordane, and methoxychlore induced the activity of NADPH-cytochrome c reductase by 45, 62, and 43 respectively after repeated dose treatments. In addition, single and repeated-dose treatments of mice with lindane induced: (i) cytochrome P450 by 23 and 65%, respectively, (ii) cytochrome b5 by 49 and 131%, respectively, (iii) AHH activity by 64 and 50%, respectively. Repeated-dose treatments of mice with chlordane, methoxychlore, and heptachlor epoxide decreased the GSH level by 42, 38, and 68%, respectively and GST activity by 44, 44, and 55% respectively. Moreover, single- and repeated-dose treatments of mice with lindane decreased the GSH levels by 40 and 54%, respectively, and induced GST activity by 25 and 41%, respectively. Interestingly, single-dose treatments with chlordane, methoxychlore, and heptachlor epoxide decreased the activity of GR by 32, 38, and 31, respectively whereas repeated doses of these compounds induced such activity by 83, 50, and 64%, respectively. It is concluded that modifications in cytochrome P450 system by pesticides could potentiate the toxicity and carcinogenicity of environmental carcinogens such as polycyclic aromatic hydrocarbon and N-nirosodimethylamine (NDMA).