Changes in glucose metabolism and reversion of genes expression in the liver of insulin-resistant rats exposed to malathion. The protective effects of N-acetylcysteine.

Organophosphorus pesticides are known to disturb glucose homeostasis and increase incidence of metabolic disorders and diabetes via insulin resistance. The current study investigates the influence of malathion on insulin signaling pathways and the protective effects of N-acetylcysteine (NAC). Malathion (200 mg/kg) and NAC (2 g/l) were administered orally to rats, during 28 consecutive days. Malathion increases plasma glucose, plasma insulin and glycated hemoglobin levels. Further, we observed an increase of insulin resistance biomarkers and a decrease of insulin sensitivity indices. The GP, GSK3ß and PEPCK mRNA expressions were amplified by malathion while, the expression of glucokinase gene is down-regulated. On the basis of biochemical and molecular findings, it is concluded that malathion impairs glucose homeostasis through insulin resistance and insulin signaling pathways disruptions in a way to result in a reduced function of insulin into hepatocytes. Otherwise, when malathion-treated rats were compared to NAC supplemented rats, fasting glucose and insulin levels, as well as insulin resistance indices were reduced. Furthermore, NAC restored liver GP and PEPCK expression. N-acetylcysteine showed therapeutic effects against malathion-induced insulin signaling pathways disruption in liver. These data support the concept that antioxidant therapies attenuate insulin resistance and ameliorate insulin sensitivity.

Effects of Rosmarinus officinalis L. as essential oils or in form of leaves supplementation on goat's production and metabolic statute.

The effects of rosemary supply in form of essential oils (REO) or leaves (RL) on performances of goats were investigated. Thirty goats were allocated into three equal groups, which were fed oat-hay ad libitum and 400 g of concentrate during the two last weeks of pregnancy and 600 g during the first 8 weeks of lactation. Three-control diet (C) was a mixture of barley, soybean meal and mineral vitamin supplement. The experimental concentrates contained the same mixture of the control diet plus 0.6 g/kg of REO or its equivalent supply RL (60 g/kg). Rosemary supply did not affect dry matter (DM), organic matter (OM), crude protein (CP) and neutral detergent fiber (NDF) digestibility. While urinary nitrogen loss was higher for experimental groups than the C (P = 0.03). Daily milk production was significantly higher (P = 0.007) for rosemary groups (694 and 582 ml for RL and REO, respectively) than C group (442 ml). Rosemary decreased numerically (P > 0.05) the fat content (23, 25 and 26.5 g/l for REO, RL and C groups, respectively) but significantly increased the fat (P = 0.003) and protein content (P = 0.008). The growth rate of kids was significantly higher (P = 0.008) for RL (111 g) than that for REO and C (97 and 83 g, respectively). However, rosemary has not shown significant effect on the plasma metabolite concentrations. Given the facility to obtain the rosemary leaves, this form of rosemary use is recommended as natural alternative to improve the performances of goats.

Antioxidant and anti-inflammatory effects of N-acetylcysteine against malathion-induced liver damages and immunotoxicity in rats.

AIMS: Occupational exposure to organophosphate pesticides is becoming a common and increasingly alarming world-wide phenomenon. The present study is designed to investigate the preventive effect of N-acetylcysteine on malathion-induced hepatic injury and inflammation in rats. MAIN METHODS: Adult male Wistar rats of body weight 200-230 g were used for the study. Malathion (200mg/kg b.w./day) was administered to rats by oral intubation and N-acetylcysteine (2g/l) in drinking water for 28 days. Rats were sacrificed on the 28th day, 2h after the last administration. Markers of liver injury (aspartate transaminase, alanine transaminase, alkaline phosphatase and lactate desyhdogenase), inflammation (leukocyte counts, myeloperoxidase, immunophenotyping of CD4(+) and CD8(+), interleukin-1ß, interleukin-6 and interferon-γ expression) and oxidative stress (lipid peroxidation, reduced glutathione and antioxidant status) were assessed. KEY FINDINGS: Malathion induced an increase in activities of hepatocellular enzymes in plasma, lipid peroxidation index, CD3(+)/CD4(+) and CD3(+)/CD4(+) percent and pro-inflammatory cytokines, when decreased antioxidant status in liver was noted. When malathion-treated rats were compared to NAC supplemented rats, leukocytosis, T cell count and IL-1ß, IL-6, INF-γ expression were reduced. Furthermore, NAC restored liver enzyme activities and oxidative stress markers. SIGNIFICANCE: Malathion induces hepatotoxicity, oxidative stress and liver inflammation. N-acetylcysteine showed therapeutic effects against malathion toxicity.