Carnitine, apelin and resveratrol regulate mitochondrial quality control (QC) related proteins and ameliorate acute kidney injury: role of hydrogen peroxide.

Mitochondrial impairment is recognised as a prominent feature in kidney diseases. Therefore, we investigated whether the effects of resveratrol, L-carnitine, and apelin in the acute kidney injury model were associated with modulation of mitochondrial quality control (QC) related proteins, intra-renal renin-angiotensin (RAS) activity, adenosine triphosphate (ATP) and Na+-K+ ATPase gene expression. Rats were randomly assigned to 7 groups: Distilled water injected control group, DMSO injected control group, distilled water injected lipopolysaccharide (LPS) group, DMSO injected LPS group, resveratrol injected LPS group, L-carnitine injected LPS group and apelin 13 injected LPS group. We observed that resveratrol, L-carnitine, and apelin treatments altered mitochondrial (QC) related protein levels (Pink1, Parkin, BNIP-3, Drp1, and PGC1α), decreased intra-renal RAS parameters, increased ATP level and upregulated Na+-K+ ATPase gene expression in renal tissue. Our results provide new insight into the role of mitochondrial quality control and how different antioxidants exert beneficial effects on acute kidney injury.

22-oxacalcitriol prevents acute kidney injury via inhibition of apoptosis and enhancement of autophagy.

BACKGROUND: The pathophysiology of ischemic acute kidney injury (AKI) is thought to include a complex interplay between tubular cell damage and regeneration. Several lines of evidences suggest a potential renoprotective effect of vitamin D. In this study, we investigated the effect of 22-oxacalcitriol (OCT), a synthetic vitamin D analogue, on renal fate in a rat model of ischemia reperfusion injury (IRI) induced acute kidney injury (AKI). METHODS: 22-oxacalcitriol (OCT) was administered via intraperitoneal (IP) injection before ischemia, and continued after IRI that was performed through bilateral clamping of the renal pedicles. 96 h after reperfusion, rats were sacrificed for the evaluation of autophagy, apoptosis, and cell cycle arrest. Additionally, assessments of toll-like receptors (TLR), interferon gamma (IFN-g) and sodium-hydrogen exchanger-1 (NHE-1) were also performed to examine their relations to OCT-mediated cell response. RESULTS: Treatment with OCT-attenuated functional deterioration and histological damage in IRI induced AKI, and significantly decreased cell apoptosis and fibrosis. In comparison with IRI rats, OCT + IRI rats manifested a significant exacerbation of autophagy as well as reduced cell cycle arrest. Moreover, the administration of OCT decreased IRI-induced upregulation of TLR4, IFN-g and NHE-1. CONCLUSION: These results demonstrate that treatment with OCT has a renoprotective effect in ischemic AKI, possibly by suppressing cell loss. Changes in the expression of IFN-g and NHE-1 could partially link OCT to the cell survival-promoted effects.

Possible involvement of tetrahydrobiopterin in the disturbance of redox homeostasis in sepsis - Induced brain dysfunction.

BACKGROUND AND AIM: Tetrahydrobiopterin (BH4) is an essential co-factor that regulates nitric oxide (NO) and reactive oxygen species (ROS) production by nitric oxide synthases (NOS). In this study, we evaluated the effects of sepsis on BH4 level and redox status in the brain by using the rat model of sepsis-induced by cecal ligation and puncture (CLP) and examined whether BH4 and/or acetyl-L-carnitine (ALC) could prevent the neuronal apoptosis and neurological changes induced by sepsis. MATERIAL AND METHOD: Male albino rats were randomly and blindly divided into 8 groups: sham, sham + BH4, sham + ALC, sham +BH4+ ALC, CLP, CLP + BH4, CLP + ALC, and CLP+BH4+ ALC. We measured neurological indicators, brain levels of BH4, guanosine triphosphate cyclohydrolase (GTPCH), sepiapterin reductase (SR) and dihydropteridine reductase (DHPR) genes expression (Essential enzymes in BH4 biosynthesis and recycling pathways). We investigated also brain redox status and both endothelial and inducible NOS expressions. RESULTS: Brain of septic rats demonstrated a reduced BH4 bioavailability, downregulation of BH4 synthetic enzymes, increased production of hydrogen peroxide and impaired antioxidant enzymes activities. Treatments with BH4 and/or ALC increased BH4 level, upregulated BH4 synthetic enzymes expressions, and attenuated oxidative-induced neuronal apoptosis. CONCLUSION: Our results suggest that BH4 and/or ALC might protect the brain against oxidative stress induced neuronal apoptosis by restoring bioavailability of BH4 and upregulating of BH4 synthetic enzymes in the brain during sepsis.

Enhancement of Neural Stem Cells after Induction of Depression in Male Albino Rats (A histological & Immunohistochemical Study).

BACKGROUND AND OBJECTIVES: Depression is one of the most prevalent psychiatric disorders. Endogenous neural stem cells (NSCs) could replace damaged Hippocampal neurons in depression. This work was planned to evaluate Rhodiola rosea (Rr) extract possible role in stimulation of NSCs proliferation and in depression improvement. METHODS AND RESULTS: Thirty adult male albino rats were divided into three groups; control, untreated depressed model and Rr model. After depression induction by chronic mild stress, rats received Rr extract 1.5 g/kg/day for three weeks. The sucrose preference test (SP) was done before, after depression induction and 3 weeks after supplementation of Rr. The brain was removed and processed for H&E and immunohistochemical staining for caspase 3, glial fibrillary acid protein (GFAP) and proliferating cell nuclear antigen (PCNA). Rr group revealed improved sucrose preference, increased undamaged neurons and decreased dark neurons. Moreover, Caspase 3 +ve cells were not detected, GFAP +ve cells increased and PCNA +ve cells were detected only in Rr group. CONCLUSIONS: This work points to the role of Rr in depression improvement and in stimulation of NSCs proliferation.