Morin inhibits oxidative stress and inflammation in the cardiorenal system associated with post-traumatic stress and alcohol use disorders in mice

Alcohol use and traumatic events have a connecting relationship owing to the rising number of people adopting alcoholism as a coping strategy. This study examined the cardiorenal protective effect of morin, a bioflavonoid, in mice comorbidly exposed to alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD). Mice exposed to single-prolong-stress (SPS)-induced PTSD were submitted to every-other-day ethanol (2 g/kg, oral gavage) for AUD induction, alongside treatments with morin (50 mg/kg and 100 mg/kg) or fluoxetine (10 mg/kg), from days 8–21 once daily. After that, mice were euthanized on day 22, markers of oxidative stress (glutathione, catalase, superoxide dismutase, malondialdehyde, nitrite) and inflammatory cytokines (tumor necrosis factor (TNF-α), interleukin-6 (IL-6)) in the kidney and heart were assayed. Our result showed that mice exposed to SPS+EtOH-induced PTSD-AUD had reduced levels of glutathione, catalase, and superoxide dismutase, with increased malondialdehyde and nitrite concentrations in the heart and kidney relative to SPS+EtOH group. Also, the SPS+EtOH group showed increased concentrations of TNF-α and IL-6 in the heart and kidney tissues, suggesting inflammatory activity relative to normal control. Treatment with morin (50 mg/kg and 100 mg/kg) significantly reduced the SPS-EtOH-induced oxidative and nitrergic stress relative to the SPS+EtOH group. Additionally, the increased release of TNF-α and IL-6 following PTSD-AUD induction was profoundly inhibited by morin in a similar manner to fluoxetine. Our findings suggest that AUD-PTSD interaction-induced organ dysfunction, such as cardiorenal impairments, was reversed by morin via mechanisms associated with attenuation of oxidative/nitrergic stress and release of pro-inflammatory cytokines in mice.