Fibromyalgia (FM) is a chronic and debilitating condition characterized by diffuse pain, often associated with symptoms such as fatigue, cognitive disturbances, and mood disorders. Metformin, an oral hypoglycemic agent, has recently gained attention for its potential benefits beyond glucose regulation. It has shown promise in alleviating neuropathic and inflammatory pain, suggesting that it could offer a novel approach to managing chronic pain conditions like FM. This study aimed to further explore metformin’s analgesic potential by evaluating its effects in an experimental FM model induced by reserpine in both male and female mice. After the administration of 200 mg/kg metformin to male and female mice, the FM-related symptoms were assessed, including mechanical allodynia, thermal hyperalgesia, and depressive-like behaviors. A histological examination of the thalamus, hippocampus, and spinal cord was conducted using haematoxylin and eosin staining. The neurotransmitter and proinflammatory cytokines levels were measured in the brains and spinal cords. Our results have shown that metformin treatment for seven days significantly reversed these FM-like symptoms, reducing pain sensitivity and improving mood-related behaviors in both the male and female mice. Additionally, metformin exhibited neuroprotective effects, mitigating reserpine-induced damage in the hippocampus, thalamus, and spinal cord. It also significantly lowered the levels of the proinflammatory cytokine interleukin 1-beta (IL-1β) in the brain and spinal cord. Notably, metformin modulated the neurotransmitter levels differently between the sexes, decreasing glutamate and increasing serotonin and norepinephrine in the male mice, but not in the females. These findings underscore metformin’s potential as an alternative therapy for FM, with sex-specific differences suggesting distinct mechanisms of action.

The liver is almost unique in its capacity for regeneration after hepatectomy but the exact mechanisms are not yet fully clarified. Antioxidants have been shown to promote liver regeneration after major hepatectomy. The present study evaluated the ameliorative effect of vitamin E administration on the liver regeneration after different periods of partial hepatectomy (PH) in rats. Fifty-six adult male albino rats were divided into three groups: Control sham operated group; partially hepatectomized group which were divided into three subgroups sacrificed at 1day, 3 days and 7days after the operation respectively; Partially Hepatectomized group with vitamin E pretreatment before PH where the rats were given a daily oral dose of vitamin E until the time of sacrifice of the rats. Immunohistochemical detection of proliferating cell nuclear antigen (PCNA) and labeling index were demonstrated. After PH, the PCNA positive hepatocytes and the PCNA labeling indices were significantly high after the 1st day and then much decreased after the 3rd day, to be followed by a slight increase at the 7th day. Vitamin E pretreatment in PH rats resulted in a decrease in PCNA positive cells and its labeling indices in the 1st day with a gradual increase in the 3rd and 7th days. Vitamin E has an inhibitory effect in the first 24 hours on liver regeneration followed by stimulatory effect at the third and seventh days after PH. These data indicated that vitamin E pretreatment has an important role in regulation and enhancement of liver regeneration after PH.