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Parkinson's disease (PD) is a motor system disorder caused by factors that lead to depletion of dopamine from the dopaminergic neurons in the substantia nigra. Mechanisms of PD include mitochondrial dysfunction, oxidative stress and neuroinflammation. Metformin is an old antidiabetic drug that has recently been shown to offer protective effects against many types of cancer, cardiovascular and neurodegenerative diseases. Indole-3-carbinol (I3C) is a phytochemical derived from the cruciform vegetables. Recently, I3C was proven to have antioxidant, anti-inflammatory and neuroprotective properties. The aim of this work was to study the effect of metformin and/or I3C on 6-hydroxydopamine (6-OHDA)-induced PD in rats. Sixty male Wistar rats were divided into 6 equal groups: Control; 6-OHDA, metformin + 6-OHDA; I3C + 6-OHDA; carboxymethyl cellulose + 6-OHDA and metformin + I3C + 6-OHDA group. Striatal dopamine, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), transforming growth factor beta1 (TGF-β1), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione reductase (GR), mitochondrial complex 1 activity, total swim score and catalepsy score were measured. The striatum was subjected to immunohistochemical examination. The combination between metformin and I3C induced significant increase in striatal SOD, GR, mitochondrial complex 1 activity and dopamine with significant decrease in striatal TNF-α, IL-6, TGF-β1, MDA and nuclear factor kappa-B expression with significant improvement in catalepsy and total swim scores better than the groups that received either I3C or metformin alone. So, metformin/I3C combination may represent a beneficial therapeutic modality for amelioration of 6-OHDAinduced PD in rats..

Background: Alzheimer's disease (AD) is a progressive neuropsychiatric disorder that causes dementia. It mostly affects people older than 65 years. The exact mechanisms of AD are not fully understood but affection of apoptosis, oxidative stress and neuroinflammation may be contributing factors. Aim: To evaluate the ability of sitagliptin and/or calcipotriol to attenuate lipopolysaccharide (LPS)-induced AD in mice and to elucidate their possible mechanisms of action. Methods: Sixty male Balb/c mice were divided into 6 equal groups: Control; LPS; LPS + carboxymethyl cellulose; LPS + Sitagliptin; LPS + Calcipotriol; and LPS + Sitagliptin + Calcipotriol group. Behavioral tests, tissue catalase (CAT), superoxide dismutase (SOD) and thiobarbituric acid derivatives (TBARS) were assessed. Also, tissue transforming growth factor beta-1 (TGF-β1), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were determined. Parts of the hippocampus were subjected to histopathological, immunohistochemical and electron microscopic examination. Results: Administration of sitagliptin and/or calcipotriol prior to LPS injection induced significant increase in the recognition index, tissue CAT and SOD associated with significant decrease in tissue TBARS, TNF-α, IL-6 and TGF-β1 and significant improvement of the histopathological, immunohistochemical and electron microscopic picture compared to LPS group. These changes were significant in sitagliptin/calcipotriol combination group compared to the use of each of these drugs alone. Conclusion: Sitagliptin/calcipotriol combination might represent a new therapeutic modality for amelioration of Alzheimer's disease.

Bisphenol-A (BPA) is a chemical substance that is widely used in industry for manufacturing of plastic bottles and resins. Recent reports found that BPA may mimic the effects of estrogen to a great manner that might disrupt the normal hormonal balance in the human body. Fluvastatin is an agent used for treatment of hypercholesterolemia that was proven to possess promising antioxidant ant anti-inflammatory properties. Taxifolin is a polyphenolic compound with potential antioxidant and antiestrogenic effects. The present study investigated the prospect of fluvastatin with or without taxifolin to mitigate testicular dysfunction elicited by BPA in rats. In a model of BPA-induced testicular toxicity, the hormonal profile was assessed and the testicular tissues were examined by biochemical analysis, histopathology, and immunohistochemistry. Fluvastatin with or without taxifolin improved the body weight gain, hormonal profile, testicular weight and functions, sperm characteristics, the antioxidant status, and the anti-inflammatory mechanisms together with enhancement of autophagy and suppression of the proapoptotic events induced by BPA in the testicular tissues. In addition, fluvastatin with or without taxifolin significantly mitigated the histopathological and the immunohistochemical changes induced by BPA in the testicular tissues. These desirable effects were more pronounced with fluvastatin/taxifolin combination relative to the use of each of these agents alone. In tandem, fluvastatin/taxifolin combination might counteract the pathogenic events induced by BPA in the testicular tissues which may be considered as a novel strategy for amelioration of these disorders.

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