Administration of hemin ameliorates ovarian ischemia reperfusion injury via modulation of heme oxygenase-1 and p-JNK/p-NF-κBp65/iNOS signaling pathway.

AIMS: Ovarian torsion is the fifth common gynecological emergency that can affect females of all ages particularly during reproductive age and its management by detorsion leads to ovarian ischemia reperfusion (IR) injury. Therefore, prophylactic measures are required to protect the ovarian function after detorsion. So that, our study aimed to assess the effect and underlying mechanisms of heme oxygenase-1 (HO-1) inducer; hemin against ovarian damage induced by IR injury in rats. MAIN METHODS: Female rats were divided into: sham group, hemin group, ovarian IR (OIR) groups with and without hemin treatment. Serum levels of reduced glutathione (GSH) and interleukin 1 ß (IL-1ß) were measured in addition to ovarian levels of malondialdehyde (MDA), nitric oxide (NO) and superoxide dismutase (SOD). Ovarian phospho-Janus kinase (p-JNK) levels and gene expressions of HO-1 and inducible nitric oxide synthase (iNOS) were determined. Moreover, histopathological changes and expressions of phospho-nuclear factor kappa B p65 (p-NF-κB p65) and cleaved caspase-3 were done. KEY FINDINGS: Treatment of OIR rats with hemin led to significant attenuation of ovarian damage through histological examination which was associated with significant increase in ovarian expression of HO-1, ovarian SOD and serum GSH levels with significant decrease in ovarian p-JNK levels, expressions of p-NF-κB p65, iNOS and cleaved caspase-3 in addition to serum IL-1ß levels. SIGNIFICANCE: The protective effect of hemin can be attributed to the increased expression of HO-1 which showed antioxidant, anti-inflammatory and anti-apoptotic effects. Therefore, hemin can be administered to prevent ovarian IR injury which occurs after detorsion.

Protective effect of hydrogen sulfide against stress-induced lung injury: involvement of Nrf2, NFκB/iNOS, and HIF-1α signaling pathways.

Stress is a common phenomenon that is attracting increasing attention. Hydrogen sulfide (H2S) is a gasotransmitter that plays an important role in many physiological and pathological events. Our study aimed to estimate the effect and the underlying mechanisms of the H2S donor, sodium hydrosulfide (NaHS), against immobilization stress (IS)-induced lung injury. Forty adult male rats were classified into control group, NaHS group, and IS groups with and without NaHS treatment. Serum was obtained to determine corticosterone (CORT), total antioxidant capacity (TAC), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) levels. Lung H2S, nitric oxide (NO), inducible nitric oxide synthase (iNOS), and malondialdehyde (MDA) levels were measured. Lung expressions of H2S synthesizing enzymes and Western blot analysis of nuclear factor erythroid 2-related factor 2 (Nrf2) and hypoxia-inducible factor 1 alpha (HIF 1α) were estimated. Histopathological changes and immunohistochemical assessment of nuclear factor kappa B (NF-κB) and caspase-3 were also done. Pretreatment with NaHS led to marked histological protection from lung damage seen in IS rats. Furthermore, pretreatment with NaHS before IS protected lung H2S levels and expressions of H2S-synthesizing enzymes. Similarly, the levels of CORT, TNF-α, IL-10, MDA, TAC, NO, iNOS, HIF-1 α, and nuclear Nrf2 and expressions of NF-kB and caspase 3 were all maintained at near control levels in contrast to that in the IS rats. In conclusion, NaHS is protective against stress-induced lung injury due to its antioxidant, anti-inflammatory, anti-fibrotic, and antiapoptotic effects. Thus, NaHS can be used to minimize stress complications on lung.

Underlying mechanisms behind the protective effect of angiotensin (1-7) in experimental rat model of ovarian ischemia reperfusion injury.

AIMS: Ovarian ischemia as a consequence of torsion constitutes a gynecologic emergency affecting females during reproductive age. Its management by detorsion results in ovarian ischemia-reperfusion (IR) injury. Thus, a conservative treatment with detorsion is highly recommended. Therefore, we attempted to investigate the effect and underlying mechanisms of angiotensin 1-7 (Ang-(1-7)) treatment against ovarian IR injury. MAIN METHODS: Female rats were included into: Sham group; Ang-(1-7) (300 µg/kg, i.p.) group; ovarian IR groups with and without Ang-(1-7) treatment. We determined ovarian Ang-(1-7), malondialdehyde (MDA) and nitric oxide (NO) in addition to serum total anti-oxidant capacity (TAC) levels. Ovarian gene expressions of angiotensin converting enzyme 2 (ACE2), Mas receptor, tumor necrosis factor alpha (TNF-α) and B-cell leukemia/lymphoma-2 (BCL-2) were estimated. Furthermore, histopathological changes and ovarian expressions of nuclear factor kappa B (NF-κB), inducible and endothelial nitric oxide synthases (iNOS and eNOS) were done. KEY FINDINGS: Treatment of ovarian IR rats with Ang-(1-7) led to marked improvement of ovarian damage through histological examination which was accompanied with marked increase in ovarian Ang-(1-7) level and expressions of ACE2 and Mas receptor, decrease in MDA and NO levels and expressions of NF-kB, iNOS and TNF-α with increase in serum TAC levels and ovarian expressions of eNOS and BCL-2. SIGNIFICANCE: Our results proved the protective effect of Ang-(1-7) against ovarian IR injury in rats and this may be attributed to ACE2/Ang (1-7)/Mas axis which showed anti-oxidant, anti-inflammatory and anti-apoptotic effects. Therefore, Ang-(1-7) can be used in the future for treatment of ovarian IR injury.