Capsaicin protects against septic acute liver injury by attenuation of apoptosis and mitochondrial dysfunction.

Capsaicin is the main pungent bioactive constituent in red chili with promising therapeutic properties due to its anti-oxidative and anti-inflammatory effects. No evidence exists on the beneficial effect of capsaicin on apoptosis and mitochondrial function in acute liver injury (ALI) under septic conditions. For inducing septic ALI, lipopolysaccharide (LPS, 50 µg/kg) and d-galactose (D-Gal, 400 mg/kg) was intraperitoneally injected and capsaicin was given orally at 5 or 20 mg/kg. Functional markers of liver function and mitochondrial dysfunction were determined as well as hepatic assessment of apoptotic, oxidative, and inflammatory factors. Capsaicin at the higher dose appropriately decreased serum level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in addition to reducing hepatic level of malondialdehyde (MDA), reactive oxygen species (ROS), nitrite, NF-kB, TLR4, IL-1ß, TNF-α, caspase 3, DNA fragmentation and boosting sirtuin 1, Nrf2, superoxide dismutase (SOD) activity, and heme oxygenase (HO-1). These beneficial effects of capsaicin were associated with reversal and/or improvement of gene expression for pro-apoptotic Bax, anti-apoptotic Bcl2, mitochondrial and metabolic regulators PGC-1α, sirtuin 1, and AMPK, and inflammation-associated factors. Additionally, capsaicin exerted a hepatoprotective effect, as revealed by its reduction of liver histopathological changes. These findings evidently indicate hepatoprotective property of capsaicin under septic conditions that can be attributed to its down-regulation of oxidative and inflammatory processes besides its potential to attenuate mitochondrial dysfunction and apoptosis.

Therapeutic effect of lycopene in lipopolysaccharide nephrotoxicity through alleviation of mitochondrial dysfunction, inflammation, and oxidative stress.

BACKGROUND: Sepsis-associated acute kidney injury (AKI) accompanies a higher mortality in intensive care patients. High-dose lipopolysaccharides (LPS) as an endotoxin is usually used to model AKI in rodents. Lycopene is a fat-soluble carotenoid with proved protective effects in different condition. Rationale and purpose of the study. This research work was designed to assess the effect of lycopene in LPS murine AKI. METHODS AND RESULTS: LPS was injected (intraperitoneally) at 10 mg/kg to induce AKI and lycopene was given (orally) at 5 or 20 mg/kg. Pretreatment of LPS group with lycopene (20 mg/kg) lowered serum BUN, creatinine, and cystatin C and alleviated renal indices of oxidative stress consisting of malondialdehyde and reactive oxygen species and elevated level of catalase activity, superoxide dismutase activity, and glutathione peroxidase activity. In addition, lycopene (20 mg/kg) attenuated renal neutrophil infiltration and reduced renal inflammation, improved mitochondrial membrane potential, and increased gene expression for PGC1-α as a key regulator of mitochondrial biogenesis. In addition, lycopene appropriately reduced level and gene expression of inflammation-related transcription factors including NF-kB and TLR4 and improved level and gene expression of Nrf2 as an important transcription factor related to antioxidant system. Besides, lycopene prevented histopathological changes following LPS in periodic acid-Schiff staining. CONCLUSIONS: Collectively, this study revealed that lycopene has favorable effects by means of amelioration of mitochondrial dysfunction, oxidative stress, and inflammation and accordingly could protect against LPS-induced AKI.

S-allyl cysteine protects against lipopolysaccharide-induced acute kidney injury in the C57BL/6 mouse strain: Involvement of oxidative stress and inflammation.

Sepsis is a serious and life-threatening medical condition with a higher rate of patients' morbidity and mortality and with complications such as acute kidney injury (AKI). S-allyl cysteine (SAC) is the active constituent of the medicinal plant garlic (Allium sativum) with multiple beneficial effects including anti-inflammatory and antioxidant properties. In this research, we tried to determine the protective effect of SAC pretreatment in a mouse model of AKI. To induce AKI, lipopolysaccharide (LPS) was injected once (10 mg/kg, i.p.) and SAC was administered at doses of 25, 50, or 100 mg/kg (p.o.) 1 h before LPS. Treatment of LPS-challenged C56BL/6 animals with SAC lowered serum level of creatinine and blood urea nitrogen (BUN), partially restored renal oxidative stress-related biomarkers including malondialdehyde (MDA), glutathione (GSH), and activity of superoxide dismutase (SOD) and catalase in addition to improvement of mitochondrial membrane potential (MMP). Furthermore, SAC was capable to bring renal nuclear factor-kappaB (NF-κB), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), toll-like receptor 4 (TLR4), cyclooxygenase-2 (COX2), tumor necrosis factor α (TNFα), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), Annexin V, and DNA fragmentation partially back to their control levels. Additionally, SAC pretreatment was capable to exert a protective effect, as shown histologically by lower tubular injury and pathologic changes in the kidney. In summary, SAC is capable to alleviate LPS-induced AKI through mitigation of renal oxidative stress, inflammation, and apoptosis in addition to preservation of mitochondrial integrity and its favorable effect exhibits a dose-dependent pattern.