Abstract
Methamphetamine (METH) is a major psychostimulant drug of abuse worldwide, and its neurotoxicity has been studied extensively. In addition to neurotoxicity, METH can also induce hepatotoxicity. The underlying mechanism of intestinal microorganisms in METH-induced hepatotoxicity remains unclear. In this study, mice have received antibiotics intragastrically or PBS once each day for 1 week, followed by METH or saline. The antibiotics attenuated METH-induced hepatotoxicity as evidenced by histopathological observation and biochemical analysis; furthermore, they alleviated METH-induced oxidative stress. The effect of antibiotics on METH-induced hepatotoxicity was investigated using RNA-sequencing (RNA-seq). The RNA-seq results demonstrated that antibiotics could regulate 580 differentially expressed genes (DEGs), of which 319 were upregulated after METH treatment and then downregulated with antibiotic pretreatment and 237 were first downregulated after METH administration and then upregulated after antibiotic pretreatment, in addition to 11 upregulated and 13 downregulated ones simultaneously in METH and antibiotic-pretreated groups. RNA-seq analyses revealed that TLR4 is one of the hub genes. Western blot analysis indicated that antibiotics inhibited the increase of TLR4, MyD88 and Traf6 induced by METH. This research suggests that antibiotics may play an important role in preventing METH-induced liver injury by regulating oxidative stress and TLR4/MyD88/Traf6 axis, though further investigation is required.
Highlights
Abuse of METH has become a major worldwide health problem (Xu et al, 2019; Xu and Liu, 2019)
Histopathological analysis revealed that karyopyknosis and extensive cytoplasmic damage in METH-treated mice were ameliorated by antibiotic pretreatment (Figure 1C)
It has been confirmed that METH induces hepatotoxicity in humans, rats, and cells (Dias Da Silva et al, 2013; Zhao et al, 2020; Zhang et al, 2021)
Summary
Abuse of METH has become a major worldwide health problem (Xu et al, 2019; Xu and Liu, 2019). METH is harmful to multiple organs (e.g., the brain, heart, liver, lung, kidney, and spleen), and the current research mainly focuses on its neurotoxicity (Liu et al, 2017; Moratalla et al, 2017; Zhang et al, 2017; Yang et al, 2018), and METH-induced hepatic injury has recently been studied (Dias Da Silva et al, 2013; Halpin et al, 2013). Previous studies found that globulin increased, albumin decreased, and albumin/globulin decreased in METH-abuser serum, indicating that METH would induce hepatic disease and inflammation (Zhao et al, 2020). Preconditioning of chlorogenic and caftaric acids could prevent liver toxicity and oxidative stress induced by METH injections (Koriem and Soliman, 2014). Our team demonstrated that METH induced hepatotoxicity by inducing cell cycle arrest and activating apoptosis (Wang et al, 2017) and luteolin exerted protective effects against METH hepatotoxicity by suppressing apoptosis, autophagy, and inflammation in rats (Qu et al, 2020; Zhang et al, 2021)
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