Eplerenone reduces renal ischaemia/reperfusion injury by modulating Klotho, NF-κB and SIRT1/SIRT3/PGC-1α signalling pathways.

OBJECTIVES: Acute kidney injury (AKI) is a sudden impairment in kidney function that is associated with high morbidity and mortality. Inflammation, oxidative stress, mitochondrial impairment and energy depletion, along with organ dysfunction are hallmarks of AKI. This study aimed to evaluate the effects of Eplerenone, an aldosterone receptor antagonist, on the kidney injury caused by ischaemia/reperfusion (I/R). METHODS: Male Wistar rats (n = 24) were randomly allocated into four groups: sham, IR, Eplerenone and Eplerenone+IR. Rats in the two last groups 1 h before I/R induction, were treated with Eplerenone (100 mg/kg) via intraperitoneal injection. Protein levels of Klotho, heat shock protein 70 (HSP70), sirtuin1 (SIRT1), SIRT3 and peroxisome proliferator-activated receptor-gamma coactivator 1-α (PGC-1α) along with antioxidant, apoptotic (caspase 3, Bax and Bcl2) and inflammatory [nuclear factor kappa-B (NF-κB) p65, Interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2)] factors were evaluated in the kidney tissues of the experimental groups. KEY FINDINGS: Eplerenone pre-treatment significantly could improve IR-induced pathological changes and kidney function and increase the renal antioxidant factors compared to the IR group (P < 0.05). Furthermore, in the Eplerenone + IR group, significant elevation of the Klotho, SIRT1, SIRT3 and PGC-1α at the protein level was identified compared to the IR group. Eplerenone pretreatment could not only downregulate NF-κB signalling and its downstream inflammatory factors (IL-6, COX-2 and TNF-α) but also could decrease apoptotic factors (P ≤ 0.01). CONCLUSIONS: The results recommended that Eplerenone exerts a protective effect against kidney IR injury by up-regulating Klotho, HSP70, sirtuins and PGC-1α to preserve mitochondrial function and cell survival. Moreover, it hinders renal inflammation by suppressing NF-κB signalling. These results offer insight into the prevention or treatment of AKI in the future.

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.

Comparative study of gavage and intraperitoneal administration of gamma-oryzanol in alleviation/attenuation in a rat animal model of renal ischemia/reperfusion-induced injury.

OBJECTIVES: Ischemia/reperfusion (I/R) is the leading cause of acute kidney injury. This study aimed to elucidate the reno-protective effect of gamma-oryzanol (GO) by comparing gavage and intraperitoneal (IP) administration methods on renal I/R injury in a rat model. MATERIALS AND METHODS: Rats were divided into four groups including (group 1) sham, (group 2) I/R-control, (group 3) I/R+GO gavage-treated, and (group 4) I/R+ GO IP-treated. A single dose of GO was administrated to groups 3 and 4 (100 mg/kg body weight), 60 min before induction of I/R. After anesthesia, I/R was created by 45 min of ischemia, followed by 6 hr of reperfusion. Then, blood and tissue samples were subjected to evaluation of renal function, anti-oxidant capacity, inflammation, apoptotic proteins, and IKB/NF-kB pathway. RESULTS: The two GO administration methods showed improvement of renal function along with attenuation of histological abnormalities. An increase in antioxidant capacity along with a decrease in pro-inflammatory markers, decline in the expression levels of BAX, Bax/Bcl-2, and caspase-3, and up-regulation of Bcl-2 expression were recorded. Moreover, a significant decrease in NF-Kb, p-IKBα, and MMP-2/9 with an increase in IKBα levels were also observed. Overall, in a comparative evaluation between the two gavage and IP administration methods, we did not find any differences in all examined parameters, except IL-6 which had a better result via gavage. CONCLUSION: A single dose of GO administration has a reno-protective effect against renal I/R injury. Gavage and IP administration exhibit similar efficiency in alleviation of I/R injury.

Current progress in cancer immunotherapy based on natural killer cells.

One of the most common diseases in the present era is cancer. The common treatment methods used to control cancer include surgery, chemotherapy, and radiotherapy. Despite progress in the treatment of cancers, there still is no definite therapeutic approach. Among the currently proposed strategies, immunotherapy is a new approach that can provide better outcomes compared with existing therapies. Employing natural killer (NK) cells is one of the means of immunotherapy. As innate lymphocytes, NK cells are capable of rapidly responding to cancer cells without being sensitized or restricted to the cognate antigen in advance, as compared to T cells that are tumor antigen-specific. Latest insights into the biology of NK cells have clarified the underlying molecular mechanisms of NK cell maturation and differentiation, as well as controlling their effector functions through the investigation of the ligands and receptors engaged in recognizing cancer cells by NK cells. Elucidating the fact that NK cells recognize cancer cells could similarly show the mechanism through which cancer cells possibly avoid NK cell-dependent immune surveillance. Additionally, the expectations for novel immunotherapies by targeting NK cells have increased through the latest clinical outcomes of T-cell-targeted cancer immunotherapy. For this emerging method, researchers are still attempting to develop protocols for conferring the best proliferation and expansion medium, activation pathways, utilization dosage, transferring methods, as well as reducing possible side effects in cancer therapy. This study reviews the NK cells, their proliferation and expansion methods, and their recent applications in cancer immunotherapy.

Salvia officinalis hydroalcoholic extract improved reproduction capacity and behavioral activity in rats exposed to immobilization stress.

This study was conducted to evaluate the Salvia officinalis hydroalcoholic extract on fertility capacity and behavioral features in rats exposed to immobilization stress. Male rats were randomly divided into five groups; Control; Stressed rats; and Stressed rats received 50, 100 and/or 200 mg/kg bw S. officinalis hydroalcoholic extract. To induce stress, rats were immobilized for 49 days and received S. officinalis extract orally. On day 56, we analyzed behavioral tests and evaluated reproduction capacity by measuring LH, FSH, and testosterone. Sperm parameters such as motility, viability, and total count were also determined. Bodyweight changes were also calculated on day 56. Male rats from different groups were mated with healthy female rats. Data showed that the use of 100 and 200 mg/kg bw S. officinalis extract in stressed rats increased bodyweight gain and improved behavioral disorders compared to control-matched groups (p < .05). Besides, administration of 100 and 200 mg/kg bw S. officinalis extract had the potential to improve sperm parameters and fertility capacity in stressed rats (p < .05). Decreased testosterone levels were blunted in the stressed rats that received plant extract coincided with the reduction of LH and FSH compared to control-matched stressed rats (p < .05). We found neutral effects in stressed rats that received 50 mg/kg bw plant extract. Collectively, the hydroalcoholic extract of S. officinalis could improve the fertility capacity and behavioral features under stressful conditions in a dose-dependent manner.