Protective effect of Eprosartan against ischemic acute renal injury: Acting on NF-κB, caspase 3, and Sirtuin 1.

Kidney ischemia/reperfusion (I/R) injury is a leading cause of acute kidney injury (AKI) occurring frequently under major surgeries and sepsis. This study aimed to evaluate the effect of Eprosartan, an angiotensin II receptor type-1 (AT-1) antagonist, on the kidney I/R rat model. Male Wistar rats (n = 24) were allocated into (i) Sham, (ii) Eprosartan, (iii) I/R, and (iv) Eprosartan + I/R groups. Animals in the last group received a single dose of Eprosartan (60 mg/kg) 1 h before kidney I/R. Renal oxidant/antioxidant, inflammatory (NF-κB p65, COX-2, IL-6, TNF-α), and apoptotic (caspase-3, Bax, Bcl2) factors along with Sirtuin 1, Klotho, and mitochondrial biogenesis (PGC-1α, and Sirtuin 3) factors were evaluated by Western blotting. Significant recovery of kidney function and increased levels of antioxidant markers were observed in the Eprosartan + I/R group. The Eprosartan anti-inflammatory activity was demonstrated by significant downregulation of NF-κB and its downstream pro-inflammatory factors. Eprosartan pretreatment could also abolish I/R-induced alterations in the apoptotic parameters. Moreover, Eprosartan + I/R rats significantly presented higher levels of Sirtuin 1 content. In conclusion, Eprosartan exhibited nephroprotective effects against kidney damage induced by I/R in rats by decreasing oxidative stress, inflammatory, and apoptotic pathways along with increasing Sirtuin1 level.

Protective effects of Gamma Oryzanol on distant organs after kidney ischemia-reperfusion in rats: A focus on liver protection.

BACKGROUND: Acute kidney injury (AKI) is the main clinical concern resulted from ischemia-reperfusion injury (IRI). Ample clinical data indicates that AKI is associated with distant organ dysfunctions and poor patients' outcomes. Oxidative stress and inflammation have a critical role in the pathogenesis of organ injuries following IRI. The objectives of this study were to determine the impact of Gamma Oryzanol (GO), extracted from rice bran oil, on distant organs in rats after IRI. METHODS: Twelve out of 24 Wistar rats were treated by one dosage of GO (100mg/kg) 1 h before I/R induction through both oral gavage and intraperitoneal injection. Then, the AKI model rats were induced by IRI. Oxidative stress and antioxidant protein levels were assessed in the brain, heart, and liver tissues in the experimental groups. Furthermore, the effects of GO on IRI-induced liver dysfunction, apoptosis, and inflammation were measured by Western blot. RESULTS: GO pretreatment could significantly restore the levels and activity of antioxidant proteins in the brain, heart, and liver tissues (P < 0.05). Moreover, GO pretreatment could decrease the inflammatory cytokine (IL-1, IL-6, and TNF-α) in the liver (P < 0.01). By reducing Bax/Bcl-2 ratio and down-regulating caspase-3, GO could significantly diminish apoptosis in the liver tissue after the kidney I/R (P < 0.01). Additionally, GO could significantly diminish the deterioration of liver function in the kidney I/R model. CONCLUSION: GO protects distant organs against renal IRI-induced oxidative stress. Furthermore, it ameliorates liver function and remarkably exerts anti-oxidative, anti-inflammatory, and anti-apoptotic roles in the liver as an important detoxifying organ.

Hepatoprotective effects of sericin on aging-induced liver damage in mice.

Aging is a physiological process in which there is a progressive decline of function in multiple organs such as the liver. The development of natural therapies, such as sericin, for delaying age-associated diseases is of major interest in this regard. Twenty-seven mice were divided into three groups of nine, including young control group (8 weeks, received normal saline), aged control group (24 months, received normal saline), and sericin-treated aged mice (24 months, received sericin at dose 100 mg/kg/day) via oral administration for 14 days. The liver enzymes in serum and oxidative stress markers in liver tissue were evaluated using spectrophotometric/ELISA methods. Apoptotic proteins, pro-inflammatory cytokines, COX2, JNK, and P-38 levels were assessed by western blot analysis. ß-galactosidase expression was determined by a qRT-PCR method. The findings showed that 100 mg/kg of sericin reduced liver enzymes in aged mice. Antioxidant capacity in treated aged mice showed an improvement in all indexes in the liver tissue. Also, sericin administration declined pro-inflammatory markers to varying degrees in aged-treated mice. Sericin also increased the expression level of Bcl-2 and decreased the expression level of Bax and cleaved caspase-3.In addition, treatment with sericin suppressed protein expression of p-JNK and p-JNK/JNK. Collectively, these findings would infer that sericin administration may have a hepatoprotective effect in aging-induced liver damage in mice.