A.A. Newairy

Biochemical study on the effects of some Egyptian herbs in alloxan-induced diabetic rats

The present study was carried out to investigate the effects of Lupinus albus, L. (Lupinus termis), family L. leguminosae, Cymbopogon proximus, (Halfa barr), family Gramineae, and Zygophyllum coccineum L. (Kammun quaramany), family L. Zygophyllacae on biochemical parameters in alloxan-induced diabetic rats. A dose of 1.5 ml of aqueous suspension of each herb/100 g body weight (equivalent to 75 mg/100 g b.wt.) was orally administered daily to alloxan-diabetic rats for 4 weeks. The levels of glucose, urea, creatinine and bilirubin were significantly (P<0.05) increased in plasma of alloxan-diabetic rats compared with the control group. In contrast, total protein and albumin were significantly decreased by 25 and 46%, respectively, versus control. Treatment of the diabetic rats with repeated doses of any one of the three herb suspensions could restore the changes of the above parameters to their normal levels after 4 weeks of treatment. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and alkaline phosphatase (AlP) activities were significantly (P<0.05) increased in the plasma of alloxan-diabetic rats. However, acetylcholinesterase activity was significantly (P<0.05) decreased in the plasma compared with the control group, whereas, such activity did not change in brain. The activities of AST, ALT and LDH were significantly (P<0.05) decreased in the liver of alloxan-diabetic rats by 58, 21 and 40%, respectively, and such activities increased in testes by 39, 26 and 26%, respectively, compared with the control group. Also, brain LDH was significantly (P<0.05) increased. Treatment of the diabetic rats with the aqueous suspension of the tested herbs restored the activities of the above enzymes to their normal level in plasma, liver and testes. The present results showed that the herb suspensions exerted antihyperglycemic effects and consequently may alleviate liver and renal damage caused by alloxan-induced diabetes.

Protective effect of ginger extract against bromobenzene-induced hepatotoxicity in male rats

The bromobenzene (BB)-induced hepatotoxicity comes from its reactive metabolites. The efficacy of different doses of ginger (Zingiber officinalesRose) extract in alleviating hepatotoxicity was investigated in male albino rats. Oxidative stress parameters were monitored. The drugs metabolizing enzymes; cytochrome P450 and GST, pro-inflammatory marker; COX-2 and the apoptotic marker; caspase-3 were assessed. Animals were assigned to 1 of 5 groups: control group; bromobenzene (460 mg/kg BW) alone, three animal groups 3-5 treated with different doses of ethanolic ginger extract (100, 200, 300 mg/kg BW, respectively) 2 weeks prior bromobenzene (460 mg/kg BW) treatment. Rats received orally ginger extract daily for 21 days whereas bromobenzene treatment for 7 days starting from 15th day of treatment. Oral treatment of BB was found to elicit a significant decrease in the activities of the antioxidant enzymes; SOD, GPx and the GSH level, while the activities of GR and drug metabolizing enzymes; GSTs and Cyt P450 were enhanced. Also, BB-treatment resulted in a great enhanced production of nitric oxide products and activation of COX-2 and caspase-3. Pre-treatment with different doses of ginger extract prior to BB-treatment alleviated its toxic effects on the tested parameters in the three animal groups.

Protective role of flax lignans against lead acetate induced oxidative damage and hyperlipidemia in rats.

The results showed that the lead concentration was higher than Cr, Ni and Cd in roadside soil samples. Also, the present study was conducted to investigate the protective role of flax lignans against the effects of lead acetate on oxidative stress, antioxidant enzymes and lipid profile. Animals were divided into three groups; the first group was used as control. While, groups 2, and 3 were orally treated with 200 mg/L lead acetate in drinking water and the combination of lead acetate (200 mg/L) plus flax lignans (30 mg/100 g BW), respectively. Rats were administered their respective doses daily for 3 weeks. Results showed that lead acetate increased TBARS, and decreased the activities of GST, SOD, GR and CAT, and the contents of glutathione in liver extracts, compared to control. The present data indicated that total lipids, cholesterol, triglycerides and LDL-c were significantly increased by lead acetate treatment, while HDL-c levels were decreased in the serum and liver extracts. Animals treated with flax lignans in combination with lead acetate alleviated its toxic effects in the tested parameters. Also, the morph metric analysis of the dorsal aorta revealed that, the histological alterations induced after lead acetate treatments were markedly reduced.

Effect of some hypoglycemic herbs on the activity of phase I and II drug-metabolizing enzymes in alloxan-induced diabetic rats

Polycyclic aromatic hydrocarbons (PAHs) and N-nitrosamines (NNA) are mainly activated by cytochrome P450s, and their associated enzyme activities such as aryl hydrocarbon (benzo(a)pyrene) hydroxylase (AHH), N-nitrosdimethylamine N-demethylase I (NDMA-dI), NADPH-cytochrome C reductase, and detoxified by glutathione S-transferase (GST) and glutathione (GSH). The present study shows the influence of Cymbopogon proximus (Halfa barr), Zygophyllum coccineum L. (Kammun quaramany), Lupinus albus (Termis) as herbs capable of inducing hypoglycemia on the activity of the above mentioned enzymes in the liver of diabetic rats. Alloxan was administered as a single dose (120 mg/kg body weight) to induce diabetes and the herbs were administered to diabetic rats as repeated doses for 4 weeks. Alloxan-induced diabetes significantly increased the blood glucose level by 93% compared to the control level. On the other hand, repeated-dose treatments of diabetic rats with Cymbopogon proximus and Lupinus albus are more effective than Zygophyllum coccineum in restoring the elevated blood glucose level to the normal level. Alloxan treatment increased the hepatic activity of cytochrome P450, NADPH-cytochrome C reductase, AHH, NDMA-dI, GST and GSH by 112, 122, 82, 99, 64 and 26%, respectively. These herbs decreased the activity of above mentioned enzymes in the liver of diabetic rats compared to alloxan-treated rats. We conclude that alloxan increased the activity of cytochrome P450 system and that such herbs reduced these activities. The toxic effects of PAHs (e.g. benzo(a)pyrene) and NNA (e.g. N-nitrosdimethylamine) could be increased in the liver of diabetic rats through induction of their corresponding bioactivating enzymes. On the other hand, hypoglycemic herbs could alleviate the deleterious effects of these carcinogens in the liver of diabetic rats since these herbs reduced the hepatic content of cytochrome P450 and other associated enzyme activities compared to the diabetic group. Such alterations in the activity of phase I and II drug-metabolizing enzymes should be considered when therapeutic drugs are administered to diabetic patients since most of drugs are metabolized mainly by the cytochrome P450 system.

Spermatotoxicity, biochemical changes and histological alteration induced by gossypol in testicular and hepatic tissues of male rats

Gossypol acetic acid (GAA) displays anti-fertility and antioxidant behavior. The efficacies of different doses of gossypol acetic acid were investigated in male albino rats. Rats were allocated into four groups: control group and three GAA-treated groups (2-4), that were injected with GAA (5, 10, 20mg/kg BW, respectively), through inrtaperitonial injection. Treatment of GAA was found to elicit a significant decrease in sperm counting, sperm motility, serum levels of testosterone, luteinizing hormone and follicle-stimulating hormone, whereas, the activities of testicular 17β-hydroxysteroid dehydrogenase and 17-ketosteroid reductase were increased. The activities of serum transaminases and alkaline phosphatase and hepatic glutathione peroxidase; glutathione reductase, superoxide dismutase and glutathione S-transferase and the level of hepatic glutathione were elevated. While, the lipid peroxidation end product; malondialdehyde, nitric oxide, and lipid profile and the activity of hepatic cytochrome P450 were decreased in GAA-treated rats. The histological analysis of liver and testicular tissues showed sever hepatocyte damage in addition to abnormal localization of hepatocytic nuclei. Also, the testicular pathology of GAA-treated rats showed depressed spermatogensis, sertoli cell toxicity and degeneration of seminiferous tubules.

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 Termis 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.

Changes in Oxidative Stress and Antioxidant Enzyme Activities in Streptozotocin-Induced Diabetes Mellitus in Rats: Role of Alhagi maurorum Extracts.

Alhagi maurorum (camel thorn plant) is a promising medicinal plant due to the presence of flavonoids and phenolic compounds as major contents of its constituents. No previous study has been conducted before on A. maurorum extracts as an antioxidative stress and/or antidiabetic herb in STZ-induced DM in rats. Therefore, four groups of rats were allocated as control (C), STZ-induced DM (D), and STZ-induced DM supplemented with 300 mg/kg BW of either aqueous extract (WE) or ethanolic extract (EE) of A. maurorum. The plasma levels of glucose, TG, TC, LDL-C and VLDL-C, MDA, and bilirubin and the activities of transaminases and GR were significantly increased in the diabetic group. Also, diabetic rats showed severe glucose intolerance and histopathological changes in their livers. In addition, levels of insulin, total proteins, GSH, and HDL-C and the activities of SOD, GPx, and GST were significantly decreased in the diabetic rats compared to those of the control group. The ingestion of A. maurorum extracts lowered the blood glucose levels during the OGTT compared to the diabetic rats and restored all tested parameters to their normal levels with the exception of insulin level that could not be restored. It is concluded that A. maurorum extracts decreased elevated blood glucose levels and hyperlipidemia and suppressed oxidative stress caused by diabetes mellitus in rats.

Aluminum-induced molecular neurodegeneration: The protective role of genistein and chickpea extract

Neurotoxicity of Al is well established and linked to oxidative damage and neurodegeneration. This study investigated the protective role of genistein (Gen) and chickpea extract (CPE) against AlCl3-induced neurodegeneration. HPLC analysis revealed that biochanin A-7-O-β-D-glucoside and biochanin A are the major components of the CPE. Gene expression of TNF-α, APP, BACE1, PSEN-2 and ER-β were assessed in brain extract using RT-PCR. Also, NF-кB subunit P65 and COX-2 expression were evaluated by western blotting. The cholinergic function, histological examination and oxidative status were also estimated. The AlCl3 significantly up regulated the expression of the NF-кB subunit P65, COX-2, TNF- α, BACE1and APP while it significantly down regulated PSEN-2 and ER-β expression. The activity of acetyl cholinesterase (AChE) and the oxidative stress parameters as well as the histological examination confirmed the deleterious effect of AlCl3. The administration of either CPE or Gen attenuated the expression of inflammatory cytokines, inhibited the amyloidogenesis and restored both the AChE activity and ER-β expression. Gen and CPE also inhibited the oxidative stress and ameliorated the histological alterations. Accordingly, the present study provides an insight on the molecular role of Gen and CPE as protective agents against neuronal injury.

Mitigating potential of Ginkgo biloba extract and melatonin against hepatic and nephrotoxicity induced by Bisphenol A in male rats

Abstract Bisphenol A is one of the anthropogenic chemicals produced worldwide, currently released into the environment and causes endocrine-disruption. The largest environmental compartments of BPA are abiotic associated with water and suspended solids that becomes an integrated part of the food chain. The present study aimed to examine the possible protective role of Ginkgo biloba extract (GBE), melatonin and their combination against BPA-induced liver and kidney toxicity of male rats. Fifty rats were divided into five equal groups: control, BPA, BPA plus GBE, BPA plus melatonin and BPA plus GBE plus melatonin. The elevated activities of plasma ALT and AST in addition to increased levels of urea and creatinine concomitant with the decreased total plasma protein could reflect the injurious effect of BPA. Liver and kidney levels of TBARS were significantly increased, while GSH, SOD and GPX were decreased in BPA-treated rats. Also, CAT and GST activities were significantly disrupted in the liver and kidney of rats treated with BPA. Moreover, BPA significantly increased the proinflammatory cytokine TNF-α in the liver and kidney tissues. The histopathological analysis confirmed these results. All the previous alterations in the liver and kidney could be ameliorated when BPA-treated rats were co-administrated either with GBE, melatonin or their combination. These natural substances could exhibit protective effects against BPA-induced hepato- and nephrotoxicity owing to their antioxidative and anti-inflammatory potentials.

Bromobenzene-induced hepatotoxicity in male rats: the protective effect of flaxseed

The metabolites of bromobenzene (BB) are hepatotoxic. The aim of this study was to determine the efficacy of different doses of flaxseed extract in alleviating BB-hepatotoxicity in male albino rats. Oxidative stress parameters, drug metabolizing enzymes, a pro-inflammatory marker, an apoptotic marker, and DNA fragmentation pattern were also assessed. Animals were divided into five groups treated by intragastric intubation as follows: control, BB-treated 460 mg kg−1 BW alone; three animal groups (III, IV, V) were treated concurrently with 460 mg kg−1 BB daily for 3 weeks and different doses of flaxseeds extract: 100, 200, or 300 mg kg−1 BW. Oral treatment of BB produced a significant decrease in activities of antioxidant enzymes superoxide dismutase and glutathione peroxidase and glutathione levels, while activities of glutathione reductase and drug-metabolizing enzymes; glutathione-S-transferases and cytochrome P450 were enhanced. BB-treatment resulted in enhanced production of nitric oxide and activation of COX-2 and caspase-3. Pre-treatment with different doses of flaxseeds extract prior and during BB-treatment protected liver against BB-induced hepatotoxicity. The lower dose of flaxseed extract (100 mg kg−1) was most effective one.