Adiponectin, insulin and nitric oxide levels in hyperlipidemia and hypercholesterolemia in addition to streptozotocin-indined diabetes mellitus and normal rats intraperitonially injected with anthocyanin and epicatechin extracts

Normal and streptozotocin-induced diabetic rats were intraperitonially injected with hibiscus anthocyanin [90 mg/Kg bw] and green tea epicatechin [60 mg/Kg bw] extracts daily for two weeks. In addition, normal and diabetic rats were force fed on high-fat diet for two weeks. Rats suffering from hypercholesterolemia were used for induction of diabetes mellitus and fed on a hypercholesterolemic diet for two weeks using non-diabetic hypercholesterolemic rats as positive control. At the end of the experiment, serum glucose insulin, adiponectin, nitric oxide and lipid profile were measured. Anthocyanin and epicatechin extracts significantly decreased the elevated levels of glucose, nitric oxide, triglycerides, total cholesterol and LDL-C in serum of diabetic rats, while adiponectin was slightly increased. The concentrations of serum glucose, nitric oxide, triglycerides, total cholesterol and LDL-C were greatly increased, while adiponectin level was significantly decreased in diabetic rats fed high-fat or high-cholesterol diets. These results indicate that increased nitric oxide and [or] decreased adiponectin in serum may result in increasing the glucose, triglycerides, total cholesterol and LDL-C levels in diabetic, hyperlipidemic and hypercholesterolemic rats

Toxicity of dibromoacetonitrile in isolated rat colonocytes

Dibromoacetonitrile [DBAN] is a water disinfection by-product. The objective of the present work was to investigate the cytotoxic effects as well as the oxidative stress induced by DBAN in cultured rat colonocytes. Colonocytes were exposed in-vitro to different concentrations of DBAN [0.1-2.0 mM] for 60 min. Also, colonocytes were incubated with DBAN [1.0 mM] for different time intervals extending to 180 min. Cytotoxicity was determined by assessing cell viability and lactate dehydrogenase [LDH] release, glutathione [GSH] level and lipid peroxidation as indicated by thiobarbituric acid reactive substances [TBARS] production. Exposure of colonocytes to DBAN [1.0 mM] for 60 min caused nearly a 50% decrease in cell viability and induced a 3-fold increase of LDH leakage. In the same experiment, DBAN caused a significant decrease in cellular GSH content as well as a significant enhancement of TBARS accumulation. These toxic responses to DBAN were dependent on both concentration and duration of exposure to DBAN. Treatment of colonocytes with GSH, N-acetyl-L-cysteine [NAC] or dithiothreitol [DTT] prior to exposure to DBAN afforded different degrees of protection as indicated by significant decrease in the LDH leakage and TBARS formation as compared to DBAN alone-treated cells. Also, pretreatment of colonocytes with the antioxidant enzymes superoxide dismutase [SOD] or catalase [CAT] significantly inhibited LDH leakage and TBARS production. Preincuhation with dimethyl sulfoxide [DMSO], a hydroxyl radical scavenger or desferroxiamine [DFO], an iron chelator, diminished DBAN-induced LDH leakage and TBARS generation. Our results suggest that DBAN has a potential cytotoxic effect in rat colonocytes; and thiol group-donors, antioxidant enzymes, hydroxyl radical scavengers and iron chelators can play an important role against DBAN-induced colonotoxicity

Dibromoacetonitrile - induced gastric toxicity in rats: role of xanthine oxidase

Dibromoacetonitrile [DBAN] is a disinfectant by-product of drinking water chlorination. Epidemiological studies indicate that exposure to haloacetonitriles via drinking water might present a potential hazard to human health. The objective of the present study was to investigate the role of xanthine oxidase [XO] I DBAN-induced toxicity in rat gastric tissues. A single oral dose of DBAN [50 mg/kg] caused a significant enhancement in XO activity. Maximum XO activity was observed at 2 h after DBAN treatment and amounted to 428% of the control enzymatic activity. DBAN also caused a significant depletion of reduced glutathione [GSH] levels and enhanced superoxide anion [O[2]] production in gastric tissues. This was accompanied by increased lipid peroxidation [determined as malondialdehyde; MDA formation] all over the time-course experiment. In addition, a dose-response experiment was established in which DBAN was given at 3 dose levels [25, 50 or 100 mg/kg]. The highest dose of DBAN [100 mg/kg] accelerated the conversion of xanthine dehydrogenase [XD] to XO; as the XO was elevated up to 35.53% compared to 7.42% of the total XD/SO activity in control rats. DBAN caused a significant depletion of gastric GSH in a dose-related manner. A strong correlation existed between the levels of GAS and the percentage enhancement in XO activity [r[2] = -0.95]. O[2] production and MDA formation were significantly elevated in a dose-related manner. To further substantiate the role of XO and GSH depletion in DBAN-induced toxiciy, the XO inhibitor; allpurinol [50 mg/kg, p.o.] or GSH-depletor, diethylmaleate [DEM, 400 mg/kg, p.o.] were given before DBAN [50 mg/kg] administration, Allopurinol significantly protected against DBAN-induced rise in XO activity depletion of GSH and elevated reduction of O[2]. Pretreatment with DEM significantly aggravated the DBAN-induced GSH depletion and rise in XO activity from 28.21% to 39.56% of the total XO/XD activity. Furthermore, DEM significantly enhanced O[2] and MDA production. The present data indicate that enhancement of XO activity is implicated in DBAN-induced gastric damage in rats