Ameliorative effect of supplementation with l-glutamine on oxidative stress, DNA damage, cell viability and hepatotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat hepatocyte cultures

Abstract

The most potent of the dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is a persistent and ubiquitous environmental contaminant. And the health impact of exposure to TCDD is of great concern to the general public. Recent data indicate that Lglutamine (Gln) has antioxidant properties and may influence hepatotoxicity. The objective of the present study was undertaken to explore the effectiveness of Gln in alleviating the hepatotoxicity of TCDD on primary cultured rat hepatocytes. Gln (0.5, 1 and 2 mM) was added to cultures alone or simultaneously with TCDD (0.005 and 0.01 mM). The hepatocytes were treated with TCDD and Gln for 48 h. Then cell viability was detected by [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] (MTT) assay and lactate dehydrogenase (LDH) release, while total antioxidant capacity (TAC), total glutathione (TGSH) and total oxidative stress (TOS) levels were determined to evaluate the oxidative injury. The DNA damage was also analyzed by liver micronucleus assay (MN) and 8-oxo-2-deoxyguanosine (8-OH-dG). The results of MTT and LDH assays showed that TCDD decreased cell viability but not L-glutamine. TCDD also increased TOS level in rat hepatocytes and significantly decreased TAC and TGSH levels. On the basis of increasing doses, the dioxin in a dosedependent manner caused significant increases of micronucleated hepatocytes (MNHEPs) and 8-OH-dG as compared to control culture. Whereas, in cultures exposured with Gln alone, TOS levels were not changed and TAC and TGSH together were significantly increased in dose-dependent fashion. The presence of Gln with TCDD modulated the hepatotoxic effects of TCDD on primary hepatocytes cultures. Noteworthy, Gln has a protective effect against TCDD-mediated DNA damages. As conclusion, we reported here an increased potential therapeutic significance of L-glutamine in TCDD-mediated hepatic injury for the first time.

Olive oil and its phenolic compounds (hydroxytyrosol and tyrosol) ameliorated TCDD-induced heptotoxicity in rats via inhibition of oxidative stress and apoptosis

“…This claim has been supported by the experimental results of various study groups in both in vitro and in vivo (Shon et al, 2002;Turkez et al, 2012). As such, there are no treatments available for the harmful effects caused by the exposure of TCDD.…”

The carvacrol ameliorates acute pancreatitis-induced liver injury via antioxidant response

“…The liver contains a number of endogenous antioxidants, to restrict steady state ROS levels (Turkez et al 2012b). The balance between ROS generation and their elimination by endogenous antioxidant mechanisms play a critical role in preserving liver function; inappropriate levels of ROS likely precipitate impairment of liver function and abnormalities in liver structure (Perez-Gutierrez and Damian-Guzman 2012).…”

Glutamine Provides Effective Protection Against Deltamethrin-Induced Acute Hepatotoxicity in Rats But Not Against Nephrotoxicity

“…Moreover, the hepatoprotective effect of GLN and its critical role in liver functions are reported [ 27 ]. Studies have found that GLN is a potent agent on the reduction of liver injury resulting from various toxic chemicals and also that GLN exerts these effects through its antioxidant effects [ 28 , 29 ]. In our study, we also found that the histopathological liver injury was significantly reduced in the DLM+GLN group.…”