Hepatoprotective and Renoprotective Effects of Lavender (Lavandula stoechas L.) Essential Oils Against Malathion-Induced Oxidative Stress in Young Male Mice.

We aimed in the present study to investigate the hepato- and nephroprotective effects of Lavandula stoechas essential oils (LSEO) against malathion-induced oxidative stress in young male mice as well as the possible mechanism implicated in such protection. Animals were divided into eight groups of 12 each: Control, malathion (200 mg/kg b.w.); Various doses of LSEO (10, 30, and 50 mg/kg b.w.), malathion+various doses of LSEO. Malathion and LSEO were daily per orally (p.o.) administered by intragastric gavage during 30 days. We initially found that malathion treatment induced body weight gain decrease as well as a clear nephro- and hepatotoxicity as assessed by significant relative liver and kidney weight increase and related hemodynamic parameters deregulation. Malathion exposure of mice also induced a considerable perturbation of metabolic parameters. On the other hand, we showed that malathion administration was accompanied by an oxidative stress status assessed by an increase of malondialdehyde (MDA) and hydrogen peroxide (H2O2) levels as well as a depletion of sulfhydril group content (-SH) and antioxidant enzyme activities such as catalase (CAT) and glutathione peroxidase (GPx), total superoxide dismutase (SOD), Cu/Zn-SOD, Mn-SOD, and Fe-SOD in the kidney and liver. More importantly, LSEO treatment abolished all malathion-induced body gain loss, liver and kidney relative weight increase, hemodynamic and metabolic disorders, as well as hepatic and renal oxidative stress. In conclusion, our data suggest that LSEO exerted potential hepato- and nephroprotective effects against malathion-induced oxidative stress in mice. The beneficial effect of LSEO might be related, in part, to its antioxidant properties.

A review on the possible molecular mechanism of action of N-acetylcysteine against insulin resistance and type-2 diabetes development.

OBJECTIVE: N-acetylcysteine (NAC), a cysteine pro-drug and glutathione precursor has been used in therapeutic practices for several decades, as a mucolytic agent and for the treatment of numerous disorders including paracetamol intoxication. There is a growing interest concerning the beneficial effects of NAC against the early stages of type-2 diabetes development. Nevertheless, the mechanisms underlying the therapeutic and clinical applications of NAC are not fully understood. In this review we aimed to focus on the protective effects of NAC against insulin resistance. DESIGN AND METHODS: The possible mechanisms of action were reviewed using the major findings of more than 100 papers relating to the antioxidant, anti-inflammatory and anti-apoptotic properties of NAC. RESULTS: The anti-oxidative activity of NAC has been attributed to its fast reactions with free radicals as well as the restitution of reduced glutathione. Further, NAC has anti-inflammatory and anti-apoptotic properties which can have positive effects during the inflammatory process in insulin resistance. Moreover, NAC can modulate certain signaling pathways in both insulin target cells and ß cells. CONCLUSIONS: The diverse biological effects of NAC may make it a potential adjuvant or therapeutic target in the treatment of type-2 diabetes. So, further studies are required for determining its ability to alleviate insulin resistance and to improve insulin sensitivity.

Protective Effect of Lavandula stoechas and Rosmarinus officinalis essential oils against reproductive damage and oxidative stress in alloxan-induced diabetic rats.

The authors aimed in the present study to assess the protective effect of Rosmarinus officinalis essential oils (ROEO) and Lavandula stoechas essential oils (LSEO) against reproductive damage and oxidative stress in alloxan-induced diabetic male rats. Essential oil samples were obtained from the aerial parts of the plants by hydrodistillation and analyzed by the gas chromatography-mass spectrometry (GC-MS). Rats were divided into four groups: healthy control (HC); diabetic control (DC); healthy+ROEO (H+ROEO), healthy+LSEO (H+LSEO), diabetic+ROEO (D+ROEO), and diabetic+LSEO (D+LSEO). The use of GC-MS allowed to the identification of 15 and 22 compounds in ROEO and LSEO, respectively. In addition, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test showed that ROEO and LSEO had an important antioxidant capacity. In vivo, we initially found that ROEO and LSEO treatment protected against the decrease in alloxan-induced body weight gain, relative reproductive organ weights, testosterone level, as well as sperm quality decline. On the other hand, we showed that alloxan administration was accompanied by an oxidative stress status assessed by an increase of malondialdehyde (MDA) and hydrogen peroxide (H2O2) levels, as well as a depletion of sulfhydril group content (-SH) and antioxidant enzyme activities as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in testis, epididymis, and sperm. More importantly, ROEO and LSEO treatment significantly protected against oxidative damage of the male reproductive organ systems in alloxan-induced diabetic rats. These findings suggested that ROEO and LSEO exerted a potential protective effect against alloxan-induced reproductive function damage and oxidative stress in male rat. The beneficial effect of ROEO and LSEO might be related, in part, to their antioxidant properties.

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.

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.

Influence of nitric oxide synthase inhibition on vasopressin and corticosterone secretion during water deprivation in rats.

Nitric oxide (NO) is a short-lived radical that functions as a neurotransmitter in the central nervous system and plays a physiological role in the regulation of hypothalamic-pituitary-adrenal axis and vasopressinergic axis. In the present study, we aimed to investigate the interaction between the generation of NO and vasopressin (AVP) and corticosterone release after 3 days of water deprivation in rats. Animals were previously treated with intraperitoneal (i.p.) saline or L-nitro-arginine methyl ester (L-NAME) injection. L-NAME is a nonspecific inhibitor of nitric oxide synthases. In control rats given i.p. saline or L-NAME, hypothalamic, pituitary, and plasma AVP levels and plasma corticosterone did not change from baseline levels (p>0.05). Three days of water deprivation increased significantly the corticosterone levels in plasma (p<0.01) and AVP levels in hypothalamus and plasma (p<0.01), but not in pituitary, which showed a significant decrease. These variations were concomitant with the elevation of nitrates/nitrates in plasma. L-NAME injection abolished significantly (p<0.01) the elevation of plasma corticosterone and hypothalamic AVP levels induced by water deprivation. These findings showed that in water-deprived rats, nitric oxide synthase inhibition by L-NAME inhibits corticosterone and vasopressin release, suggesting a potent stimulatory role of NO.

Malathion exposure modulates hypothalamic gene expression and induces dyslipedemia in Wistar rats.

Exposure to organophosphate (OP) pesticides is virtually ubiquitous. These inevitable agents are neurotoxicants, but recent evidence also points to lasting effects on carbohydrate metabolism. The aim of this study was to investigate the effects of 32 repeated treatment days with malathion, an OP insecticide, on some molecular and metabolic parameters. Malathion at 100 mg/kg was administered by gavage in Wistar rats. Results of this study indicate a significant decrease in hypothalamic corticotropin-releasing hormone mRNA, of malathion-treated rats. This result, in accordance with that of diabetic type 2 rat model, may be due to very potent negative feedback effects of glucocorticoids on hypothalamo-pituitary-adrenal (HPA) axis activity. In addition, we have recorded a significant increase in hypothalamic inducible NO synthase mRNA which probably enhances the negative feedback. These alterations are accompanied with hypertriglyceridemia that may be a favourable condition to insulin resistance. Thus, results of the present study suggest that malathion can be considered as an important risk factor in the development of diabetes type 2, which prevalence increased substantially in our country and around the world. Clearly, we need to focus further research on the specific incidences of hazardous food chemical contaminant that might be contributing to epidemic health perspectives.

Dietary virgin olive oil protects against lipid peroxidation and improves antioxidant status in the liver of rats chronically exposed to ethanol.

Excessive ethanol intake induces severe tissue damage particularly in the liver through the generation of reactive oxygen species. The aim of this study was to determine the effect of a virgin olive oil-rich diet on oxidative stress induced by chronic ethanol exposure in rats. Wistar rats were treated daily with a 35% ethanol solution for 6 weeks and fed with a standard chow or a diet containing 5% virgin olive oil. By administering ethanol to rats, a severe toxicity occurred in their liver, as assessed by the significantly elevated levels of serum transaminases. The hepatic malondialdehyde level, indicator of lipid peroxidation, was also increased in ethanol-treated rats, whereas the hepatic antioxidant enzyme activities, namely, superoxide dismutase, glutathione peroxidase, and catalase were significantly reduced. The activity of glutathione reductase remained unchanged in rats. Fatty acid composition of the liver was also significantly changed with ethanol intake. In contrast, virgin olive oil intake during ethanol treatment in rats resulted in a higher antioxidant activity and inhibited toxicity to the liver, as monitored by the reduction of transaminases levels and hepatic lipid peroxidation. Rats showed a better profile of the antioxidant system with normal glutathione peroxidase activity and ameliorated superoxide dismutase and catalase activities. In conclusion, results of this study indicate that olive oil ingestion by rats protects the liver from ethanol-induced oxidative damage by affecting the cellular redox potential.

Resveratrol, a red wine polyphenol, attenuates ethanol-induced oxidative stress in rat liver.

The involvement of oxidative stress in the pathogenesis of alcoholic diseases in the liver has been repeatedly confirmed. Resveratrol, a natural phytoalexin present in grape skin and red wine possesses a variety of biological activities including antioxidant. This study was conducted to evaluate whether resveratrol has a preventive effect on the main indicators of hepatic oxidative status as an expression of the cellular damage caused by free radicals, and on antioxidant defence mechanism during chronic ethanol treatment. Wistar rats were treated daily with 35% ethanol solution (3 g/kg/day i.p.) during 6 weeks and fed basal diet or basal diet containing 5 g/kg resveratrol. Control rats were treated with i.p. saline and fed basal diet. Experimentally, chronic ethanol administration leads to hepatotoxicity as monitored by the increase in the level of hepatic marker enzymes and the appearance of fatty change, necrosis, fibrosis and inflammation in liver sections. Ethanol also enhanced the formation of MDA in the liver indicating an increase in lipid peroxidation, a major end-point of oxidative damage, and caused drastic alterations in antioxidant defence systems. Particularly the activities of hepatic superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were found reduced by ethanol treatment while glutathione reductase (GR) activity was unchanged. Dietary supplementation with resveratrol during ethanol treatment inhibited hepatic lipid peroxidation and ameliorated SOD, GPx and CAT activities in the liver. Conclusively, we can suggest that resveratrol could have a beneficial effect in inhibiting the oxidative damage induced by chronic ethanol administration, which was proved by the experiments that we conducted on rats.