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Acute kidney injury (AKI) is a severe medical condition that can lead to illness and death. A disintegrin and metalloprotease (ADAM) protein family is a potential treatment target for AKI due to its involvement in inflammation, growth, and differentiation. While ADAM10 and ADAM17 have been identified as significant contributors to inflammation, it is unclear whether they play a critical role in AKI. In this study, we induced AKI in male and female mice using lipopolysaccharide, a bacterial endotoxin that causes inflammation and oxidative stress. The role of kaempferol, which is found in many natural products and known to have antioxidant and anti-inflammatory activity in many pre-clinical studies, was investigated through ADAM10/17 enzymes in AKI. We also investigated the efficacy of a selective synthetic inhibitor named GW280264X for ADAM10/17 inhibition in AKI. Blood urea nitrogen and creatinine levels were measured in serum, while tumor necrosis factor-α, vascular adhesion molecule, interleukin (IL)-1β, glucose regulatory protein-78, IL-10, nuclear factor κ-B, thiobarbituric acid reactive substances, total thiol, ADAM10, and ADAM17 levels were measured in kidney tissue. We also evaluated kidney tissue histologically using hematoxylin and eosin, periodic acid-schiff, and caspase-3 staining. This research demonstrates that GW280264X and kaempferol reduces inflammation and oxidative stress, as evidenced by biochemical and histopathological results in AKI through ADAM10/17 inhibition. These findings suggest that inhibiting ADAM10/17 may be a promising therapeutic approach for treating acute kidney injury., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ovarian ischemia is a gynecological emergency case that occurs as a result of ovarian torsion. Oxidative stress and inflammation play central roles in the development of ischemia/reperfusion injuries. We investigated the effects of Vitamin B12, thought to possess antioxidant characteristics on oxidative stress and the toll-like receptor 4 (TLR-4)/nuclear factorkappa B (NF-κB) signaling pathway in the ovaries during ischemia-reperfusion. Forty-eight rats were randomly assigned into six groups and the groups are designed as follows: Control (C), Ischemia (I), Ischemia + Vitamin B12 (I + B12), Ischemia-Reperfusion (I/R), I/R + Vitamin B12 (I/R + B12) and Sham + Vitamin B12. Vitamin B12 was administered at a dose of 400 mcg/kg via the i.p. route once daily for three days before I/R procedure. Tissue interleukin-1β (IL-1β) and interleukin-6 (IL-6) and malondialdehyde (MDA) levels in ovarian tissue increased following I/R, while glutathione (GSH) levels decreased. Moreover, extensive congestion, edema, hemorrhage and defective follicle were observed. Both NF-κB and TLR-4 expression levels also increased in the group exposed to I/R. While GSH levels increased, IL-1β, IL-6, MDA, NF-κB and TLR-4 levels decreased with Vitamin B12 treatment. In addition, ovarian tissue without edema, mild congestion, and normal-appearing follicles were observed following Vitamin B12 administration. The findings showed that I/R in ovarian tissue resulted in significant tissue damage by increasing oxidative stress and inflammation. However, Vitamin B12 application was effective and alternative agent in reducing injury deriving from inflammation and oxidative stress developing in association with I/R in ovarian tissue., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Damage to the ovaries or tissue torsion can significantly reduce the ovarian reserve and thus cause severe gynecological and hormonal deficiencies. The discovery of new agents is always needed in the treatment of this condition. Metformin (MET) has been shown to be beneficial in attenuating ovarian ischemia-reperfusion injury. Fifty-six female Sprague Dawley rats were divided into seven groups. Group 1 represented the control group (C), Group 2, the ischemia group (I), and Group 3, the ischemia/reperfusion group (I/R). Group 4, the ischemia (I)+250 group, and Group 5, the ischemia (I)+500 group, received 250 mg/kg and 500 mg/kg MET, respectively. Group 6, the ischemia/reperfusion (I/R)+250 group, and Group 7, the ischemia/reperfusion (I/R)+500 group, received 250 mg/kg and 500 mg/kg MET, respectively. Tissue malondialdehyde (MDA), glutathione (GSH), and tumor necrosis factor-alpha (TNF-α) levels in ovarian tissue increased following I/R, while estradiol (E 2 ) levels decreased. Moreover, infiltration and diffuse edematous areas were observed in addition to diffuse vascular congestion and hemorrhage findings. Caspase-3 and nuclear factor kappa B (NF-κβ) expression levels also increased. MDA and TNF-α concentrations decreased in the MET treatment groups, while GSH and E 2 levels increased. The findings showed that I/R causes ovarian damage through the induction of oxidative stress, inflammation, and apoptosis. However, MET application was effective in preventing damage in ovarian tissue by reducing levels of reactive oxygen species, proinflammatory cytokines, caspase-3 and NF-κβ., (Copyright © 2019 Elsevier B.V. All rights reserved.)