Ischaemia‐reperfusion (IR) is the most common form of testicular injury that results in oxidative damage and inflammation ending by subinfertility. Paeonol, a natural phenolic compound, exhibits antioxidant and anti‐inflammatory effects. Thus, the present study investigated the role of paeonol in rat testicular IR injury. Thirty adult Wistar rats were randomly divided into five groups; sham, sham treated with paeonol, IR injury, and IR pre‐treated with paeonol at low and high doses. Serum testosterone and testicular levels of malondialdehyde and reduced glutathione (GSH) besides superoxide dismutase (SOD) activity were determined. Gene quantifications for tumour necrosis factor‐α (TNF‐α), hypoxia‐inducible factor‐1α (HIF‐1α) and heat shock protein 70 (HSP70) were also assessed. Histopathological pictures and the immunohistochemical expression of testicular nuclear factor erythroid 2‐related factor 2 (Nrf2), interleukin‐1β (IL‐1β) and interleukin‐6 (IL‐6) were shown. Pre‐treatment with paeonol prevented the drop in serum testosterone, alongside with improvement of testicular malondialdehyde and GSH levels plus SOD activity. Paeonol regained the normal spermatogenesis with prevention of IR‐induced increase in TNF‐α, HIF‐1α and HSP70 gene expression besides IL‐1β and IL‐6 immunostaining and reduction in Nrf2 protein expression. Paeonol exerted a dose‐dependent beneficial effect on testicular IR injury. This effect was achieved by its antioxidant and anti‐inflammatory effects.

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Paeonol, a natural phenolic compound, possesses diverse beneficial effects including antioxidant and anti-inflammatory effects. Gastric ulcer is still the most prevalent irritant illness among the gastrointestinal diseases. The present study explored the protective effect of paeonol at two dose levels in indomethacin (IND)-induced gastric ulcer in rats. Forty-eight male Wistar rats were arranged into six groups: control, paeonol-treated, IND-treated, IND/paeonol (low and high doses)-treated, and ranitidine-treated groups. The oxidative status was evaluated by determining malondialdehyde level, superoxide dismutase activity, reduced glutathione content as well as hemoxygenase-1 (HO-1) gene expressions, and the antioxidant protein; NAD(P)H quinone oxidoreductase 1 (NQO1) immunostaining. The pro-inflammatory genes nuclear factor κB (NF-κB) and interleukin 1β (IL-1β) were estimated together with the proapoptotic gene of caspase 3. IND caused multiple gastric ulcers with evident oxidative damage and elevated pro-inflammatory and proapoptotic markers. Paeonol protected significantly, in a dose-dependent manner, the gastric mucosa from ulcerative lesion of IND similar to the reference drug ranitidine. Paeonol pretreatment diminished gastric oxidative stress and restored the gastric antioxidant capacity by elevating gastric gene expression of HO-1 and protein expression of NQO1. Paeonol also reduced NF-κB, IL-1β, and caspase 3 gene expressions. In conclusion, paeonol offered a gastroprotection dependent on its antioxidant, anti-inflammatory, and antiapoptotic effects.

The model group showed evidence of liver injury as indicated by the elevation of liver enzymes and confirmed by histopathological findings. TAA-induced liver injury was accompanied with downregulation of the cytoprotective pathways: PI3K/Akt and Nrf2/HO-1 mRNAs. Cilostazol administration ameliorated TAA-induced liver injury, where it caused a significant improvement in the activity liver enzymes as well as in the histopathological changes. Such effect was associated with a significant increase in the expression of PI3K/Akt and Nrf2/HO-1 mRNAs as detected by Real-time reverse transcription polymerase chain reaction (RT-PCR).

Endometrial hyperplasia (EH) is a medical condition that affects many females as it increases their uterine carcinogenic potential. EH results from entangling hormonal imbalance and inflammatory response. The study examined the role of a xanthine oxidase inhibitor, febuxostat, in a rat model of EH. Adult female Wistar albino rats were subjected to estradiol valerate (EV) 2 mg/kg for 10 days to induce EH. Another group was treated concomitantly with febuxostat 10 mg/kg for the same period. The uterine malondialdehyde, reduced glutathione (GSH), and superoxide dismutase (SOD) were assessed by chemical methods. Gene expressions of phosphatidylinositol-3-kinase (PI3K), Akt, and hypoxia-inducible factor 1 alpha were assessed by the quantitative real-time polymerase chain reaction. Moreover, the vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay. Histopathology and immunohistochemical techniques were used for the detection of phosphatase and tensin homolog (PTEN). The results revealed that EV administration induced complex EH with focal atypia and loss of PTEN expression by the histological examination. Uteri of the EV group showed a significant drop in GSH content and SOD activity and rise in the expressions of PI3K, Akt, VEGF, and IL-6. Febuxostat administration significantly improved the uterine GSH and SOD levels. It decreased the expressions of PI3K, Akt, VEGF, and IL-6. The endometrium showed a regression of the proliferative epithelium with the restoration of PTEN expression and the absence of the atypical features. In conclusion, febuxostat protected the endometrium against estrogen-induced EH and may be beneficial in the management along with the hormonal therapy.