The hepato-renal protective potential of walnut seed skin extract against acute renal ischemia/reperfusion damage.

Acute kidney damage is defined as a sudden change in kidney functions that prevents the removal of nitrogenous wastes from the body, thus disrupting the body's fluid and electrolyte balance. When acute kidney injury occurs, the kidneys and liver are most affected in the body. Agents used in the treatment of acute kidney injury often have nonsteroidal anti-inflammatory properties that can produce toxic effects on the gastrointestinal tract and kidneys. Natural antioxidants can be recommended as an alternative to existing treatment or in combination to protect tissues against these toxic effects. Therefore, we conducted our current study on whether walnut seed skin (WSS) extract might have hepato-renal protective effects in kidney-damaged Sprague-Dawley rats. This study is the first to use walnut seed skin extract in liver and kidney tissues in renal ischemia/reperfusion (IR) injury. Female Sprague-Dawley rats were randomly divided into three groups: Healty control (HC), renal IR (50 min ischemia - 3 h reperfusion), and renal IR + 450 mg/kg/p.o. WSS extract (the rats were treated with WSS extract orally once 1 h before the IR procedure). For this purpose, blood, liver and kidney tissues of rats were used. In serum samples, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), urea and creatinine values were determined separately for the administration groups. We also performed histopathological studies on liver and kidney tissues. Finally, gene markers (endothelial nitric oxide synthase (eNOS), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), Caspase-4 and Caspase-9) determined to evaluate the anti-oxidant, anti-inflammatory and apoptotic effect of walnut seed skin were measured by q-RT PCR method. As a result of the study it was determined that pre-application of WSS extract improved the deteriorated serum parameters in rats with renal ischemia. In the histopathological analysis results, it was observed that WSS had a protective effect on kidney and liver tissue. In studies on gene expression, although there were different and contradictory results for liver and kidney tissue, we determined that WSS was more protective on liver tissue. In conclusion, the healing potential of WSS in renal and hepatic tissues seems to act by inhibiting the inflammatory response, oxidative stress and apoptosis. Therefore, the potential of this extract is remarkable and may serve as a potential therapeutic that may protect against acute organ damages due to renal IR.

Inula graveolens induces selective cytotoxicity in glioblastoma and chronic leukemia cells.

OBJECTIVE: Crude oil extracts, components of extracts, and ethanolic extracts of Inula graveolens possess various pharmacological activities on various cancer cells including antioxidative and antiproliferative effects. Aqueous extract of this species has not been investigated on the liquid malignancies and solid tumors with a high incidence of treatment refractoriness and poor survival outcomes such as glioblastoma and leukemia. Hence, the present study aimed to evaluate the cytotoxic efficiency of I. graveolens aqueous extracts on human glioblastoma multiforme and chronic myelogenous leukemia cell lines in comparison to non-cancerous primary rat cerebral cortex and human peripheral blood mononuclear cells. METHODS: The cells were treated with the extracts of I. graveolens (125-1000 µg/mL) for 48 h, the cellular viability was identified using 3'-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and lactate dehydrogenase release was measured to determine the cytotoxic potential. Total oxidant status and apurinic/apyrimidinic endodeoxyribonuclease 1 assays were used to determine the oxidative status of cells and DNA damage, respectively. RESULTS: I. graveolens showed selective cytotoxicity toward human glioblastoma multiforme and chronic myelogenous leukemia cell lines and exhibited a higher antiproliferative effect against cancer cells in comparison to non-cancerous cells. Moreover, it significantly reduced the apurinic/apyrimidinic endodeoxyribonuclease 1 levels on both cancer cell lines as compared with their control cells without changing the levels of an oxidative stress marker. CONCLUSION: The extracts of I. graveolens have anti-cancer potential on human glioblastoma multiforme and chronic myelogenous leukemia cell lines without causing oxidative stress.

The targets of ß-sitosterol as a novel therapeutic against cardio-renal complications in acute renal ischemia/reperfusion damage.

This research is the first to use ß-sitosterol on myocardial and renal tissues in renal ischemia/reperfusion (IR) damage. Female Wistar rats were randomly divided into three groups: control (sham), renal IR (50 min ischemia - 3 h reperfusion), and renal IR + 150 mg/kg/p.o. ß-sitosterol (the rats were treated with ß-sitosterol orally once 1 h before the IR procedure). ß-Sitosterol pretreatment caused an increase in superoxide dismutase and glutathione activities and a decrease in malondialdehyde levels in the kidney and heart. Moreover, it alleviated histopathological changes and downregulated the levels of tumor necrosis factor-alpha and interleukin-6 and upregulated the levels of endothelial nitric oxide synthase. As conclusion, the potential of ß-sitosterol for renal and cardiac necrosis and apoptosis appears to act by limiting inflammatory response and oxidative stress. Thus, the potential of this compound is noteworthy and may serve as a potential therapeutic in the treatment of acute organ damages due to renal IR.

Propolis and Its Combination with Boric Acid Protect Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Inhibiting Oxidative Stress, Inflammation, DNA Damage, and Apoptosis in Rats.

Ischemia reperfusion (I/R) injury which causes kidney dysfunction is one of the most studied diseases directly linked to oxidative stress. In this regard, it is important to protect cells against damage by inducing antioxidant response. Herein, we aimed to evaluate the therapeutic roles and possible mechanisms of propolis and boric acid in kidney I/R injury based on relevant basic research and clinical studies. Sprague-Dawley rats were subjected to 50 min of ischemia followed by 3 h of reperfusion. Animals were randomly divided into a control group (the abdominal wall was just opened and closed), an I/R injury group, the propolis intervention group (200 mg/kg, intragastric administration, 1 h before ischemia), boric acid intervention group (14 mg/kg, intragastric administration 1 h before ischemia), and the propolis + boric acid intervention group (intragastric administration 1 h before ischemia). Kidney function, the antioxidant defensive system, and renal damage were assessed. In addition, the oxidative stress and inflammatory status were estimated in renal tissue. Furthermore, DNA damageand apoptosis were detected by immunohistochemistry. When compared with I/R group, propolis alone and especially propolis + boric acid groups significantly improved functional parameters. While the antioxidant response was increased, renal injury size and apoptosis were significantly decreased in both groups. Also, the MDA and TNF-α levels besides the 8-OHdG formation were downregulated. According to these outcomes, it can be said that especially propolis together with boric acid ameliorates kidney injury caused by I/R through acting as an antioxidant, anti-inflammatory, and antiapoptotic agent. In conclusion, propolis alone and its combination with boric acid could be developed as therapeutic agents against serious renal I/R injuries.

The efficacy of oleuropein against non-steroidal anti-inflammatory drug induced toxicity in rat kidney.

Indomethacin is generally used in clinical therapeutics as a non-steroidal anti-inflammatory drug. However, its use has been limited due to the gastrointestinal and renal toxic effects of this drug. These toxic effects were associated with not only the inhibition of prostaglandin synthesis but also drug-elevated oxidative stress. To ameliorate these toxicities, natural antioxidants can be used as an alternative and/or combination therapies. Therefore, the current study was conducted to assess the renoprotective effects of oleuropein against indomethacin-induced renal damages. Male Sprague-Dawley rats were pretreated with oleuropein (75, 150, and 300 mg/kg), and then treated with indomethacin (25 mg/kg). To evaluate kidney function, serum blood urea nitrogen, uric acid, and creatinine were measured. In addition, prostaglandin E2 , tumor necrosis factor-alpha, endothelial nitric oxide synthase, caspase-3, oxidant/antioxidant status, and 8-Oxo-2'-deoxyguanosine levels were determined for the antioxidative and anti-inflammatory effects of oleuropein. Tissue sections were also histopathologically assessed. The biochemical and histopathological analysis proved the toxic effects of indomethacin on kidney. However, the pretreatment with oleuropein (300 mg/kg) protects kidney from indomethacin-induced damages. Our study proved that prior administration of oleuropein has renoprotective activity against indomethacin-associated toxicities.