Mitochondrial Involvement in the Adaptive Response to Chronic Exposure to Environmental Pollutants and High-Fat Feeding in a Rat Liver and Testis

Abstract

In our modern society, exposure to stressful environmental stimuli, such as pollutants and/or chronic high-fat feeding, continuously induce tissular/organ metabolic adaptation to promote cellular survival. In extreme conditions, cellular death and tissular/organ damage occur. Mitochondria, as a cellular energy source, seem to play an important role in facing cellular stress induced by these environmental stimuli. On the other hand, mitochondrial dysfunction and oxidative stress play a key role in environmental stress-induced metabolic diseases. However, little is known about the combined effect of simultaneous exposure to chronic high-fat feeding and environmental pollutants on metabolic alterations at a tissular and cellular level, including mitochondrial dysfunction and oxidative stress induction. Our research group recently addressed this topic by analysing the effect of chronic exposure to a non-toxic dose of the environmental pollutant dichlorodiphenyldichloroethylene (DDE) associated with high-fat feeding in male Wistar rats. In this review, we mainly summarize our recent findings on mitochondrial adaptive response and oxidative stress induction in the liver, the main tissue involved in fat metabolism and pollutant detoxification, and in male gonads, the main targets of endocrine disruption induced by both high-fat feeding and environmental pollutants.

Exposure to Dichlorodiphenyldichloroethylene (DDE) and Metallothionein Levels in Rats Fed with Normocaloric or High-Fat Diet: A Review

“…Recently, histological and molecular analysis indicated that oral exposure to a moderately low dose of DDE (10 mg/kg bw) for 4 weeks was able to elicit morphological alterations, cellular oxidative stress, and lipid peroxidation in rat tissues [47,48,56,58]. Studies also evidenced the presence of similar morphological and oxidative damage caused by the fat diet alone [47,48,56,58]. In the liver, an HF diet induced steatosis of hepatocytes, and DDE treatment-tissue inflammation and cellular vacuolization.…”

“…It has been demonstrated that the presence of DDT and its metabolites in animal tissues causes oxidative stress and mitochondrial damage [43][44][45][46][47][48], whereas few data, often controversial, are available on the effects of these substances on MT expression and synthesis. A study performed by Ben Miled and coworkers [49] showed an increase in MT content in hepatocytes of rats receiving a single intraperitoneal injection of 100 mg DDT/kg body weight (bw).…”

Oxidative Stress in NAFLD: Role of Nutrients and Food Contaminants

“…For example, oxidative stress generated by exposure to the insecticide permethrin is linked to the detoxifying activities of CYP450 enzymes, and other enzymes involved in oxidation and hydrolysis processes [ 364 ]. Organochlorine compounds such as DDT lead to an increased ROS production through activation of CYP450 gene expression involved in its detoxifying pathway in exposed rat liver [ 211 ]. The biotransformation reactions of organophosphorus compounds, during which an excess of free radicals is generated, also produces ROS [ 187 ].…”

“…In fact, various chemical families of insecticides seem to be involved, i.e., organochlorine, pyrethroid, neonicotinoid, and organophosphorus compounds ( Table 2 [ 148 , 184 , 185 , 195 , 196 , 197 , 198 , 199 , 200 , 201 , 202 , 203 , 204 , 205 , 206 , 207 , 208 , 209 , 210 ]). Moreover, HFD components may act as a vehicle for pesticides, allowing them to reach target organs more easily, as proposed in [ 136 , 211 ]. This finding suggests that a different bioavailability of pesticides in mice fed with an HFD versus normal chow diet may explain, at least in part, dissimilar outcomes with pesticide exposure in different studies.…”

Early life thermal stress modulates hepatic expression of thermotolerance related genes and physiological responses in two rabbit breeds

“…However, at 13 weeks of age (Figure 4(G)) thermally conditioned rabbit in both breeds had overexpressed hepatic UCP2 compared to their control groups indicating a protective function of this overexpression and improve thermotolerance acquisition resulted from thermal conditioning at early life. The substantial role of UCP2 is to monitor mitochondria-derived ROS production (Sreedhar and Zhao 2017) and the upregulation of UCP2 may reduce ROS production due to its antioxidative protective effects (Huang et al 2019;Migliaccio et al 2019). Besides, UCP2 overexpression may enhance cytoprotection by alleviating oxidative stress (Mattiasson et al 2003) and attenuating superoxide production to protect hepatic damage in mice due to oxidative stress (Zhang et al 2003).…”