Acute Ethanol-induced Oxidative Stress Research Articles

Novel functional food from an invasive species Polygonum cuspidatum: safety evaluation, chemical composition, and hepatoprotective effects

Abstract Accidentally, we found that the shoots of Polygonum cuspidatum (SPC) have been consumed for centuries as a traditional vegetable in the Shennongjia region of China. Local residents believe that SPC has biological effects such as antibacterial, anti-aging, and antioxidant. To provide scientific support for the use of SPC as a functional food, SPC was evaluated in terms of safety, chemical composition, and antioxidant activity both in vivo and in vitro. In the first, SPC exhibited no adverse cytotoxic effects or acute toxicity in mice. Then the chemical composition of SPC was determined by ultrahigh performance liquid chromatography–electrospray ioniza­tion–quadrupole time of flight tandem mass spectrometry (UHPLC-ESI-QTOF-MS/MS). Twenty-two compounds were identified from the SPC extracts, including phenolic, flavonoid, stilbene, and anthraquinone. Finally, an acute ethanol-induced oxidative stress model in mice showed hepatoprotective effects. In brief, our study indicated that SPC is a safe, multifunctional food with antioxidant and hepatoprotective activities. Importantly, the consumption of SPC as a functional food provides a novel strategy for the efficient utilization of the invasive plant.

Methylene Blue Protects Against Acute Ethanol-Induced Oxidative Stress and Organ Damage

Ethanol (EtOH) intake is an important global health problem which affects many organs such as the brain, liver and stomach. The aim of the study was to examine the effect of the redox dye methylene blue (MethyB) on oxidative stress and histologic damage to the liver, gastric mucosa, and brain induced high dose ethanol (EtOH). Male rats were treated with EtOH (2 ml/rat, 96%) via intragastric route (for two consecutive days). MethyB (20 or 40 mg/kg, intraperitoneally) was given immediately after EtOH administration. The control group received saline. Rats were euthanized three hours after the last treatment. Brain and liver levels of malondialdehyde (MDA), reduced glutathione (GSH), and paraoxonase-1 (PON-1) as well as brain 5-lipoxygenase (5-LOX) and butyrylcholinesterase (BChE) were determined. Histopathological assessment of brain, liver and gastric damage was done. Results indicated that compared to saline treated animals, EtOH caused significant increase in MDA, along with decreased GSH and PON-1 activity in brain and liver. Additionally, it significantly increased 5-LOX and decreased brain BChE activity. The EtOH group showed the presence of dead and red neurons, and damage of glial cells. The liver exhibited vacuolar degeneration, apoptotic hepatocytes and foci of necrosis. The gastric mucosa showed areas of tissue damage, mucosal atrophy, and loss of normal architecture of glandular cells. The EtOH induced biochemical and histopathological alterations were alleviated after treatment with MethyB at a dose-dependent manner. These results demonstrate that MethyB is able to protect against from acute effects of EtOH on brain, liver and gastric tissue via an antioxidant action. MethyB might be of value in reducing tissue injury in acute EtOH intoxication.

Protective effects of rare earth lanthanum on acute ethanol-induced oxidative stress in mice via Keap 1/Nrf2/p62 activation

With the widespread application of rare earth elements (REEs) in environment safety, food and medicine, they accumulate in the ecosystem and different human organs where REEs exert certain biological effects. Low dose REEs are proved to perform antioxidant effects, while high concentration can cause oxidative stress. However, scant information about rational doses and underlying mechanism of REEs as oxidants/antioxidants were illustrated. To elucidate these problems, here we performed a study that the ICR mice were received 0.1, 0.2, 1.0, 2.0 and 20.0 mg/kg lanthanum nitrate (La(NO3)3) by gavage for 30 days, and then were given 12 mL/kg ethanol once to undergo acute ethanol-induced oxidative stress. The antioxidant enzymes, antioxidants, peroxides and related proteins in Keap 1/Nrf2/p62 signaling pathway were measured. The results showed that La(NO3)3 inhibited hepatic morphological alternations by histopathological examination. Meanwhile, elevated superoxide dismutase (SOD) and glutathione (GSH), coupled with decreased alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA) and protein carbonyl (PC) were observed in serum and liver tissues of mice by enzyme-linked immunosorbent assay test. Furthermore, western blot analysis demonstrated that oxidative stress was alleviated due to enhanced NF-E2-related factor 2 (Nrf2) and phosphorylated p62 expressions as well as lower Kelch-like ECH-associated protein-1 (Keap 1), followed by the activation of heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO-1) and glutamate cysteine ligase, catalytic (GCLC) proteins. Our findings clearly highlighted that La(NO3)3 could restore the redox homeostasis disrupted by ethanol through provoking Keap 1/Nrf2/p62 signaling pathway, and the optimal dosages were 1.0 and 2.0 mg/kg.

Ameliorative Efficacy of Phytochemical Content of Corchorus olitorius Leaves against Acute Ethanol-induced Oxidative Stress in Wistar Rats

Aim: This study is aimed at investigating the ameliorative efficacy of methanolic extract of Corchorus olitorius leaves against acute ethanol-induced oxidative stress in Wistar rats.
 Methods: Fresh plants of C. olitorius were harvested from the Institute of Agricultural Research and Training, Ibadan. The leaves were dried and extracted using soxhlet apparatus and methanol as the solvent. The methanol was evaporated in a rotary evaporator at 35°C with a yield of 2.17 g which represents a percentage yield of 8.68%. Twenty adult male Wistar rats with body weight between 120 and 150 g were used for this study. They were randomly divided into four groups of five rats each. Animals in groups 1 and 2 were administered saline solution while those in groups 3 and 4 were administered C. olitorius extract for twenty-one days. The animals were administered the extract and saline solution at a dose of 4 mL per 100 g body weight 12 hourly via oral route of administration. At the end of the treatment, they were fasted overnight and animals in groups 2 and 4 were exposed to a single dose of 70% ethanol at 12 ml/kg body weight to induce oxidative stress. After 12 hours of ethanol administration, the animals were anaesthetized using diethyl ether and were sacrificed. Liver was excised, weighed and homogenized in 50 mmol/L Tris–HCl buffer (pH 7.4) and then centrifuged at 5000 × g for 15 minutes for biochemical analysis. Supernatants were immediately kept frozen for further analysis.
 Results: Ethanol-induced oxidative stress significantly increased the activities of AST, ALT, LDH, LPO, CAT, SOD and GPX but decrease GSH. These effects were regulated by C. olitorius administration.
 Conclusion: C. olitorius was able to remedy the effect of ethanol by regulating the oxidative stress biomarkers, thus possesses ameliorative efficacy against ethanol-induced oxidative stress and can protect the body against free radicals arising from oxidative stress.

17β-Estradiol via SIRT1/Acetyl-p53/NF-kB Signaling Pathway Rescued Postnatal Rat Brain Against Acute Ethanol Intoxication.

Growing evidences reveal that 17β-estradiol has a wide variety of neuroprotective potential. Recently, it has been shown that 17β-estradiol can limit ethanol-induced neurotoxicity in neonatal rats. Whether it can stimulate SIRT1 signaling against ethanol intoxicity in developing brain remain elusive. Here, we report for the first time that 17β-estradiol activated SIRT1 to deacetylate p53 proteins against acute ethanol-induced oxidative stress, neuroinflammation, and neurodegeneration. A single subcutaneous injection of ethanol-induced oxidative stress triggered phospho c-jun N terminal kinase (p-JNK) and phospho mammalian target of rapamycin (p-mTOR) accompanied by neuroinflammation and widespread neurodegeneration. In contrast, 17β-estradiol cotreatment positively regulated SIRT1, inhibited p53 acetylation, reactive oxygen species (ROS) production, p-JNK, and p-mTOR activation and reduced neuroinflammation and neuronal cell death in the postnatal rat brain. Interestingly, SIRT1 inhibition with its inhibitor, i.e., EX527 further enhanced ethanol intoxication and also abolished the beneficial effects of 17β-estradiol against ethanol in the young rat's brain. Indeed, 17β-estradiol treatment increased the cell viability (HT22 cells), inhibited ROS production via the SIRT1/Acetyl-p53 pathway, and reduced the nuclear translocation of phospho-nuclear factor kappa B (p-NF-kB) in the BV2 microglia cells. Taken together, these results show that 17β-estradiol can be used as a potential neuroprotective agent against acute ethanol intoxication.

Hepato- and neuro-protective effects of watermelon juice on acute ethanol-induced oxidative stress in rats.

Chronic and acute alcohol exposure has been extensively reported to cause oxidative stress in hepatic and extra-hepatic tissues. Watermelon (Citrullus lanatus) is known to possess various beneficial properties including; antioxidant, anti-inflammatory, analgesic, anti-diabetic, anti-ulcerogenic effects. However, there is a lack of pertinent information on its importance in acute alcohol-induced hepato- and neuro-toxicity. The present study evaluated the potential protective effects of watermelon juice on ethanol-induced oxidative stress in the liver and brain of male Wistar rats. Rats were pre-treated with the watermelon juice at a dose of 4 ml/kg body weight for a period of fifteen days prior to a single dose of ethanol (50%; 12 ml/kg body weight). Ethanol treatment reduced body weight gain and significantly altered antioxidant status in the liver and brain. This is evidenced by the significant elevation of malondialdehyde (MDA) concentration; depletion in reduced glutathione (GSH) levels and an increased catalase (CAT) activity in the brain and liver. There was no significant difference in the activity of glutathione peroxidase (GPX) in the liver and brain.Oral administration of watermelon juice for fifteen (15) days prior to ethanol intoxication, significantly reduced the concentration of MDA in the liver and brain of rats. In addition, water melon pre-treatment increased the concentration of GSH and normalized catalase activity in both tissues in comparison to the ethanol control group. Phytochemical analysis revealed the presence of phenol, alkaloids, saponins, tannins and steroids in watermelon juice. Our findings indicate that watermelon juice demonstrate anti-oxidative effects in ethanol-induced oxidation in the liver and brain of rats; which could be associated with the plethora of antioxidant phyto-constituents present there-in.

Hepatoprotective effect of carob against acute ethanol-induced oxidative stress in rat

The present study was undertaken to determine whether subacute treatment with aqueous extract of carob (Ceratonia siliqua L.) pods (AECPs) protects against ethanol (EtOH)-induced oxidative stress in rat liver. Animals were divided into four groups: control, carob, EtOH and EtOH+carob. Wistar rats were intraperitoneally pretreated with AECP (600mg/kg body weight (bw)) during 7days and intoxicated for 6h by acute oral administration of EtOH (6g/kg bw) 24h after the last injection. We found that acute administration of EtOH leads to hepatotoxicity as monitored by the increase in the levels of hepatic marker aspartate aminotransferase and alanine aminotransferase as well as hepatic tissue injury. EtOH also increased the formation of malondialdehyde in the liver, indicating an increase in lipid peroxidation and depletion of antioxidant enzyme activities as superoxide dismutase, catalase and glutathione peroxidase. Subacute carob pretreatment prevented all the alterations induced by EtOH and returned their levels to near normal. Importantly, we showed that acute alcohol increased hepatic and plasmatic hydrogen peroxide and free iron levels. The carob pretreatment reversed EtOH effects to near control levels. These data suggest that carob could have a beneficial effect in inhibiting the oxidative damage induced by acute EtOH administration and that its mode of action may involve an opposite effect on plasma and tissue-free iron accumulation. Indeed, carob can be offered as a food additive to protect against EtOH-induced oxidative damage.