Preventive effect of methanolic extract of Zataria Multiflora Boiss on liver toxicity of paracetamol in rats.

Background: The analgesic paracetamol causes a potentially fatal, centrilobular hepatic necrosis when taken in misuse and overdose. This research aimed to evaluate the protective effects of methanolic extract of Zataria Multiflora Boiss (Z. Multiflora) against hepatic damage induced by paracetamol-induced hepatotoxicity in male Wistar rats. Methods: for this purpose, paracetamol was administrated orally at a dose of 2 g/ kg body weight (b.w.)/ day on the seventh day after the oral administration of a methanolic extract of Z. Multiflora at doses of 100 mg/ kg, 200 mg/ kg and 400 mg/ kg b.w. The lipid peroxidation level and activities of liver aminotransferases and enzymes contributing to the oxidative damage were measured in serum, and a histopathological examination of liver sections was also performed. Results and Discussion: The results showed that Z. Multiflora reduced the activity of aminotransferases in rats treated with paracetamol. This extract also inhibited lipid peroxidation and protein carbonylation by an increase in the activity of the antioxidant enzyme and the elevation of glutathione content of the liver. Conclusion: These effects are related to the antioxidant compounds of Z. Multiflora. The methanolic extract of this herb exhibits protective effects against paracetamol-induced hepatotoxicity.

Hepatoprotective effect of Zataria Multiflora Boisson cisplatin-induced oxidative stress in male rat.

Background: This research aimed to evaluate the protective effects of methanolic extract of Zataria Multiflora Boiss (Z. Multiflora) against hepatic damage induced by cisplatin in male Wistar rats. Methods: Hepatotoxicity was induced in Wistar male rats by a single intraperitoneal administration of cisplatin, 7 g/ kg body weight. A methanolic extract of Z. Multiflora was administered orally at doses of 50 mg/ kg, 100 mg/ kg, 200 mg/ kg and 400 mg/ kg body weight daily for seven days after being cisplatin-induced. The study included the histopathological examination of the liver sections. The activity of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) were evaluated as markers of liver damage. The superoxide dismutase (SOD), the activity of Catalase (CAT), and glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) and nitric oxide (NO) content in serum were measured as an oxidative stress factor. Results: The results showed that rat treated with cisplatin resulted in a significant increase in serum activity, AST, ALT and ALP in treated mice. Management with Z. Multiflora reduced the business of these enzymes to nearly normal levels. In parallel with these changes, this extract reduced cisplatin-induced oxidative stress by inhibiting lipid peroxidation and protein carbonylation, and restoring the antioxidant enzyme (SOD, CAT, and GSH-Px) and elevation of the glutathione level. Conclusion: Biochemical and histological observations showed the hepatoprotective effect was found in a dose-dependent manner in Z. Multiflora methanolic extract. This protective effect can be attributed to the antioxidant compounds.

Mechanisms of muscular electrophysiological and mitochondrial dysfunction following exposure to malathion, an organophosphorus pesticide.

Muscle dysfunction in acute organophosphorus (OP) poisoning is a cause of death in human. The present study was conducted to identify the mechanism of action of OP in terms of muscle mitochondrial dysfunction. Electromyography (EMG) was conducted on rats exposed to the acute oral dose of malathion (400 mg/kg) that could inhibit acetylcholinesterase activity up to 70%. The function of mitochondrial respiratory chain and the rate of production of reactive oxygen species (ROS) from intact mitochondria were measured. The bioenergetic pathways were studied by measurement of adenosine triphosphate (ATP), lactate, and glycogen. To identify mitochondrial-dependent apoptotic pathways, the messenger RNA (mRNA) expression of bax and bcl-2, protein expression of caspase-9, mitochondrial cytochrome c release, and DNA damage were measured. The EMG confirmed muscle weakness. The reduction in activity of mitochondrial complexes and muscular glycogen with an elevation of lactate was in association with impairment of cellular respiration. The reduction in mitochondrial proapoptotic stimuli is indicative of autophagic process inducing cytoprotective effects in the early stage of stress. Downregulation of apoptotic signaling may be due to reduction in ATP and ROS, and genotoxic potential of malathion. The maintenance of mitochondrial integrity by means of artificial electron donors and increasing exogenous ATP might prevent toxicity of OPs.

A systematic review on the nerve-muscle electrophysiology in human organophosphorus pesticide exposure.

This article presents a systematic review of the recent literature on the scientific support of electromyography (EMG) and nerve conduction velocity (NCV) in diagnosing the exposure and toxicity of organophosphorus pesticides (OP). Specifically, this review focused on changes in EMG, NCV, occurrence of intermediate syndrome (IMS), and OP-induced delayed polyneuropathy (OPIDN) in human. All relevant bibliographic databases were searched for human studies using the key words "OP poisoning", "electromyography", "nerve conduction study," and "muscles disorders". IMS usually occurs after an acute cholinergic crisis, while OPIDN occurs after both acute and chronic exposures. Collection of these studies supports that IMS is a neuromuscular junction disorder and can be recorded upon the onset of respiratory failure. Due to heterogeneity of reports on outcomes of interest such as motor NCV and EMG amplitude in acute cases and inability to achieve precise estimation of effect in chronic cases meta-analysis was not helpful to this review. The OPIDN after both acute and low-level prolonged exposures develops peripheral neuropathy without preceding cholinergic toxicity and the progress of changes in EMG and NCV is parallel with the development of IMS and OPIDN. Persistent inhibition of acetylcholinesterase (AChE) is responsible for muscle weakness, but this is not the only factor involved in the incidence of this weakness in IMS or OPIDN suggestive of AChE assay not useful as an index of nerve and muscle impairment. Although several mechanisms for induction of this neurodegenerative disorder have been proposed as were reviewed for this article, among them oxidative stress and resulting apoptosis can be emphasized. Nevertheless, there is little synchronized evidence on subclinical electrophysiological findings that limit us to reach a strong conclusion on the diagnostic or prognostic use of EMG and NCV for acute and occupational exposures to OPs.