Saponin protects against cyclophosphamide-induced kidney and liver damage via antioxidant and anti-inflammatory actions.

Background: The liver and kidney are organs affected by chemotherapy drugs such as cyclophosphamide (CP). This study examined the protective effects of treatment with saponin (SP) against CP-induced nephrotoxicity and hepatotoxicity. Methods: 24 adult male mice were divided into four groups (N = 6): Control group, CP (15 mg kg-1), SP (2.5 mg kg-1) and CP + SP. After treatment, blood samples were collected for the determination of biochemical parameters. Liver and kidney samples were taken for histological analysis and assessment of oxidative stress and inflammatory markers. Results: Cyclophosphamide decreased renal and liver functions and antioxidant enzymes, which significantly increased blood urea nitrogen and creatinine (BUN, Cr), liver enzyme levels, malondialdehyde, nuclear factor kappa ß (NF-kB) and Interleukin 1 beta (IL-1B) concentrations. Moreover, histopathological findings of the CP group showed that there were acute tubular necrosis and glomerular atrophy in the renal tissues and lymphocyte infiltration in the liver samples. Treatment with saponin improved hepatic and renal functions, pathological changes and antioxidant capacity, and also decreased lipid peroxidation and inflammation. Conclusion: It seems that saponin could exert a hepato-nephroprotective effect against cyclophosphamide toxicity.

Inhibitory effects of Ficus carica and Olea europaea on pro-inflammatory cytokines: A review.

Objectives: Ficus carica (fig) and Olea europaea (olive) are valuable nutritional plants that are widely used in diet and traditional medicine. Different parts of the plants such as fruit and leaves contain beneficial compounds with diverse pharmacological properties, among which anti-inflammatory activities are remarkable. The purpose of this review is to discuss the anti-inflammatory effects of F. carica and O. europaea with emphasis on their impact on pivotal pro-inflammatory cytokines including IL-1, IL-6, and TNF-α. Materials and Methods: To prepare the present review, the sites utilized included Scopus, PubMed, Science Direct, and Google Scholar and studied relevant articles from 2000 until 2021. Results: As a result, we observed that most of the compounds in fig and olive including polyphenols, flavonoids, etc., exert their anti-inflammatory effects through inhibiting or decreasing pro-inflammatory cytokines. Moreover, some natural antioxidants are common between these two plants. Conclusion: We suggest that consuming figs and olives simultaneously or alone can be useful in the prevention or treatment of inflammatory diseases.

Protective effect of saponin on sperm DNA fragmentation of mice treated with cyclophosphamide.

Cyclophosphamide (CP) is a common chemotherapy drug with the testicular damage. The aim of this study was to investigate the effect of saponin (SP) on the toxicity of CP in the male reproductive system. Following an experimental pilot study for determining SP dose, 40 male mice (32 ± 3 g) were divided into five groups (n = 8): control, sham (normal saline 0.2 ml/day), CP (15 mg/kg/week, intraperitoneally), SP (2.5 mg/kg/day, intraperitoneally) and saponin group with cyclophosphamide (SP + CP). After treatment, the left testes were removed for the measurement of malonedialdehyde (MDA) and total antioxidant capacity (TAC) levels, and sperm DNA fragmentation was assessed by SDFA kit. In the CP group, a significant decrease in motility, viability, count, normal morphology and DNA fragmentation of spermatozoa and TAC was observed, while in MDA level, a significant increase was observed compared with the control group (p < 0.05). Attenuated sperm parameters in CP group improved significantly in SP + CP group (p < 0.05). According to the findings of this study, SP was able to alter the reproductive toxicity of CP in NMRI mice and increase the antioxidant capacity of the testis.

Mechanistic Evaluation of Linalool Effect against Renal Ischemia- Reperfusion Injury in Rats.

BACKGROUND: Kidney ischemia reperfusion (IR) is an important cause of renal dysfunction. The hypoxic conditions in ischemic damage result in the formation of free radicals and apoptotic death of renal cells. We evaluated the renoprotective effects of linalool in IR- induced renal injury. METHODS: Wistar rats were divided into three groups of six rats; namely, control group, IR group, and linalool + IR group. The animals were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h reperfusion. Linalool (40mg/kg) was administered before ischemia. After 24h reperfusion, the kidney tissues were obtained for detection of miR-21, HSP 70 and caspase-3 expression levels and histological studies. Also, the blood samples were collected for the measurement of biochemical parameters. RESULTS: IR significantly increased the expression of miR-21, HSP70 and capase-3 and the serum levels of BUN-Cr, ALT, AST and ALP enzymes. Furthermore, histological findings of the IR group confirmed that there were acute tubular necrosis and lymphocyte infiltration in the renal tissues. Treatment with linalool improved the renal function and morphological changes. CONCLUSION: It seems that linalool could exert a nephroprotective effect via a number of mechanisms in renal IR injury.

Vitamin D3 and erythropoietin protect against renal ischemia-reperfusion injury via heat shock protein 70 and microRNA-21 expression.

Kidney ischemia reperfusion (IR) contributes to the development of acute kidney injury. The hypoxic conditions in ischemic damage lead to oxidative stress and apoptotic cell death. We investigated the effects of vitamin D3 (Vit D) and erythropoietin (EPO) on microRNA-21(miR-21) expression in renal IR. Wistar rats were divided into five groups including the control, vehicle + IR, Vit D + IR, EPO + IR, and Vit D + EPO + IR groups. The animals were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h reperfusion. Vitamin D3 and EPO were administered prior to ischemia. After 24 h reperfusion, the kidney samples were collected for the detection of miR-21, heat shock protein 70 (hsp70) and caspase-3 expression levels. Kidney IR significantly increased the expression of miR-21, hsp70 and capase-3 and blood urea nitrogen (BUN)-Cr levels. Treatment with vitamin D3 and EPO significantly decreased the BUN-Cr levels and hsp70 and caspase-3 expression. Also, the co-administration of two drugs significantly increased miR-21 expression. It seems that vitamin D3 or EPO administration could protect the kidney against IR injury. However, vitamin D3 and EPO co-treatment was the most effective compared with the other treatment groups.

The protective effect of cinnamon and ginger hydro-alcoholic extract on carbon tetrachloride-induced testicular damage in rats.

Sexual dysfunction of men is one of the most serious problems in human society. This study aimed to evaluate the protective effect of cinnamon and ginger extract on testicular damages induced by carbon tetrachloride (CCl4). Thirty-six male Wistar rats were randomly divided into 6 groups (n = 6): 1. Normal control; 2. Carbon tetrachloride (CCl4); 3. CCl4 + Cinnamon; 4. CCl4 + Ginger; 5. CCl4 + Cinnamon and Ginger; and 6. Cinnamon + Ginger. CCl4 (1 ml/kg) was injected intraperitoneally on the 14th day, and cinnamon (50 mg/kg, orally) and ginger (250 mg/kg, orally) were administered daily for 14 days. Fifty hours after the CCl4 injection, the testicles and epididymis were separated and examined as to histological alterations and oxidative stress markers. CCl4 significantly increased malondialdehyde level and decreased total antioxidant capacity when compared to the normal control group (p < .05). In addition, degenerative alterations in the testicular and epididymal tissue were observed in CCl4 group. The pre-treatment with ginger and cinnamon extract significantly improved these parameters when compared to the CCl4 group (p < .05). The results of this study indicated that co-treatment of ginger and cinnamon reduces the damages induced by CCl4 in testicular tissue by increasing antioxidant capacity and reducing lipid peroxidation.

The role of hormones in renal disease and ischemia-reperfusion injury.

The patients with renal diseases, especially end-stage renal disease (ESRD), are at high risk of developing cardiovascular disturbances. Some hormones such as brain natriuretic peptide appear to be important serum biomarkers in predicting cardiac death in ESRD patients. Renal diseases cause inflammation, anemia, uremic toxins, fluid overload, and electrolyte disturbance. Kidney transplantation is considered the choice treatment for patients with ESRD. Ischemia-reperfusion (IR), which occurs during renal transplantation is one of the factors that affect the outcome of renal transplantation. Renal graft rejection is the result of IR injury and there is no effective treatment to prevent IR injury. Reperfusion after ischemia may cause injury through generation of reactive oxygen and nitrogen species, inflammatory responses by increased levels of tumor necrosis factor-α (TNF-α) and interleukins (IL), and apoptotic processes, and leads to acute kidney injury (AKI). Thus, antioxidant, anti-apoptotic and anti-inflammatory hormones, which inhibit these pathways, can protect against IR injury and improve transplanted renal function in patients with ESRD.

Renoprotective effects of the methanolic extract of Tanacetum parthenium against carbon tetrachloride-induced renal injury in rats.

OBJECTIVE: Studies have demonstrated that carbon tetrachloride (CCl4) increases the generation of reactive oxygen species (ROS) in many tissues including the kidney, heart, lung, brain, and liver. The major aim of the present study was to evaluate the protective activity of Tanacetum parthenium extract (TPE) in renal tissues of CCl4-intoxicated rats. MATERIALS AND METHODS: Animals were divided into seven groups of six rats. Group 1 was the control group that was not treated with CCl4. The rats in the other groups were intraperitoneally injected with CCl4 (1.5 ml/kg, 1:1 in olive oil) on day 14. Rats in the groups bTPE40, bTPE80, and bTPE120 were gavaged with 40, 80, and 120 mg/kg of TPE, respectively for 14 constitutive days on a daily basis, before CCl4 administration. Rats in groups aTPE80 and aTPE120 were gavaged with 80 and 120 mg/kg of TPE, respectively, 2, 6, 24 and 48 hr after receiving CCl4. Blood samples were collected at the end of the 16th day through an intracardiac puncture and then serums were separated. RESULTS: CCl4 increased urea, creatinine, uric acid and creatinine: albumin (C/A) ratio level in serum and decreased total antioxidant and antioxidant enzymes (SOD and GPx) when compared to the control group (p<0.001). But administration of TPE to rats either before or after exposure to CCl4, attenuated these changes when compared with CCl4 control group (p<0.05 - p<0.001). CONCLUSION: TPE had potent nephroprotective effects against oxygen free radicals produced through CCl4 metabolism.

Comparison of the Protective Effects of Erythropoietin and Melatonin on Renal Ischemia-Reperfusion Injury.

BACKGROUND: Renal ischemia-reperfusion (IR) contributes to the development of acute renal failure (ARF). Oxygen free radicals are considered to be the principal components involved in the pathophysiological tissue alterations observed during renal IR. OBJECTIVES: In this study, we compared the effects of melatonin (MEL) and erythropoietin (EPO), both known antioxidant and anti-inflammatory agents, on IR-induced renal injury in rats. MATERIALS AND METHODS: Wistar albino rats were unilaterally nephrectomized and then subjected to 45 minutes of renal pedicle occlusion followed by 24 hours of reperfusion. MEL (10 mg/kg, i.p) and EPO (5000 U/kg, i.p) were administered prior to the onset of ischemia. After 24 hours of reperfusion and following decapitation, blood samples were collected for the determination of the hemoglobin (Hb) and hematocrit (Hct) levels. Additionally, renal samples were taken for histological evaluation. RESULTS: Ischemia-reperfusion significantly decreased the observed Hb and Hct values. The histopathological findings in the IR group confirmed that there was an increase in the hyaline cast and thickening of the Bowman capsule basement membrane. Treatment with EPO or MEL significantly increased the Hb and Hct values. In the MEL + IR group, the histopathological changes were lower than those found in the EPO + IR group. CONCLUSIONS: Treatment with EPO and MEL had a beneficial effect on renal IR injury. The results may also indicate that MEL protects against morphological damage better than EPO in renal IR injury.

Combination Anti-Apoptotic Effect of Erythropoietin and Melatonin on Ischemia Reperfusion-Induced Renal Injury in Rats.

Renal ischemia-reperfusion (IR) contributes to the development of acute renal failure (ARF). Oxygen free radicals are considered to be principal components involved in the pathophysiological tissue alterations observed during renal IR. The purpose of this study was to investigate the combination effect of melatonin (MEL) and erythropoietin (EPO), which are a potent antioxidant and anti-apoptotic agents, in IR-induced renal injury in rats. Wistar Albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h reperfusion. MEL (10 mg/kg, i.p) and EPO (5000 U/kg, i.p) were administered prior to ischemia. After 24 h reperfusion, following decapitation, blood samples were collected for the determination of superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels. Also, renal samples were taken for histological evaluation and apoptosis assay. Ischemia-reperfusion increased SOD, GPx, MDA levels, and TUNEL positive cells. Histopathological findings of the IR group confirmed that there was renal impairment in the tubular epithelium. Treatment with EPO and MEL decreased SOD, GPx, and MDA levels, histopathological changes, and TUNEL positive cells. These results indicated that the combination of MEL and EPO could not exert more nephroprotective and anti-apoptotic effects than MEL treatment in renal ischemia-reperfusion injury.

The effect of 5-aminosalicylic acid on renal ischemia-reperfusion injury in rats.

OBJECTIVES: Ischemia-reperfusion (IR) contributes to the development acute renal failure. Oxygen free radicals are involved in the pathophysiology of IR injury (IRI). This study was designed to investigate the effects of 5-aminosalicylic acid (5-ASA), which is known antioxidant agent, in IR-induced renal injury in rats. MATERIALS AND METHODS: Male Wistar albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h of reperfusion. 5-ASA (300 mg/kg, i.p) was administered prior to ischemia. After 24 h reperfusion, urine and blood samples were collected for the determination of creatinine (Cr) and nitric oxide (NO) levels, and renal samples were taken for the histological evaluation. RESULTS: Treatment with 5-ASA significantly decreased serum Cr and NO levels, also significantly increased urinary Cr level and decreased histopathological changes induced by IR. CONCLUSION: Treatment with 5-ASA had a beneficial effect on renal IRI. These results may indicate that 5-ASA exerts nephroprotective effects in renal IRI.

Novel role of microRNAs in renal ischemia reperfusion injury.

Renal ischemia reperfusion injury (IRI) contributes to the development of acute kidney injury (AKI). Several processes are involved in the development of renal IRI with the generation of reactive oxygen species, inflammation and apoptosis. MicroRNAs (miRNAs) are endogenous, small and noncoding RNAs that repress gene expression of target mRNA in animals post-transcriptionally. miRNA-mediated gene repression is a major modulatory mechanism to regulate fundamental cellular processes such as the cell cycle, proliferation, growth, and apoptosis, which in turn have pivotal influences on pathophysiological outcomes. Recent studies have revealed the pathogenic roles played by miRNAs in many renal diseases, such as IRI, AKI and renal carcinoma. In addition, the majority of miRNAs identified appear to be differentially expressed, probably to quell the injury response by modulating inflammation, apoptosis and proliferation and may point us toward new pathways that can be targeted to regulate or prevent renal IRI. They may represent novel diagnostic biomarkers of renal IR injury.

Effect of a combined treatment with erythropoietin and melatonin on renal ischemia reperfusion injury in male rats.

BACKGROUND: Renal ischemia reperfusion (IR) is an important cause of renal dysfunction. It contributes to the development of acute renal failure. Oxidative damage from reactive oxygen species is considered to be the principal component involved in the pathophysiological tissue alterations observed during IR. The purpose of this study was to evaluate the effect of a combined treatment with erythropoietin (EPO) plus melatonin (MEL), which are known anti-inflammatory and antioxidant agents, in IR-induced renal injury in rats. METHODS: Wistar Albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h of reperfusion. MEL (10 mg/kg, i.p) and EPO (5000 U/kg, i.p) were administered prior to ischemia. After 24 h of reperfusion, blood samples were collected for the determination of superoxide dismutase (SOD), glutathione peroxidase (GPx), plasma levels of total antioxidant capacity (TAC), and malondialdehyde (MDA) and serum urea level. Also, renal samples were taken for histological evaluation. RESULTS: Ischemia reperfusion significantly increased urea, blood SOD, and GPx levels. Histological findings of the IR group indicated that there was increase in tubular and glomerular hyaline cast, thickening of Bowman capsule basement membrane, and renal impairment in the glomerular epithelium. Treatment with EPO and MEL significantly decreased blood SOD, GPx, and urea levels and increased TAC level. In the EPO + MEL group, while the histopathological changes were lower than those in EPO group, they were the same as MEL group. CONCLUSION: EPO and MEL combination treatment exerted more nephroprotective effects than EPO treatment and nearly had protective effects similar to MEL treatment.

The anti-inflammatory effect of erythropoietin and melatonin on renal ischemia reperfusion injury in male rats.

PURPOSE: Renal ischemia reperfusion (IR) is an important cause of renal dysfunction. It contributes to the development of acute renal failure (ARF). The purpose of this study was to investigate the anti-inflammatory effect of erythropoietin (EPO) and melatonin (MEL), which are known anti-inflammatory and antioxidant agents, in IR-induced renal injury in rats. METHODS: Male Wistar Albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h reperfusion. MEL (10mg/kg, i.p) and EPO (5000U/kg, i.p) were administered prior to ischemia. After 24 h reperfusion, blood samples were collected for the determination of total antioxidant capacity (TAC), malondialdehyde (MDA) and serum creatinine levels. Also, renal samples were taken for Immunohistochemical evaluation of Bcl2 and TNF-α (tumor necrosis factor-α) expression. RESULTS: Ischemia reperfusion increased creatinine, TAC, MDA levels and TNF-α expression, also, IR decreased Bcl2 expression. Treatment with EPO or MEL decreased creatinine, MDA levels, and increased TAC level. Also, MEL up-regulated Bcl2 expression and down-regulated TNF-α expression compared with EPO. CONCLUSION: Treatment with EPO and MEL had a curative effect on renal IR injury. These results may indicate that MEL protects against inflammation and apoptosis better than EPO in renal IR injury.

Combination antioxidant effect of erythropoietin and melatonin on renal ischemia-reperfusion injury in rats.

OBJECTIVE(S): Renal ischemia reperfusion (IR) contributes to the development of acute renal failure (ARF). Oxygen free radicals are considered to be principal components involved in the pathophysiological tissue alterations observed during renal IR. The purpose of this study was to investigate the effect of co-administration of melatonin (MEL) and erythropoietin (EPO), potent antioxidant and anti-inflammatory agents, on IR-induced renal injury in rats. MATERIALS AND METHODS: Wistar albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 hr reperfusion. MEL (10 mg/kg, IP) and EPO (5000 U/kg, IP) were administered prior to ischemia. After 24 hr reperfusion, following decapitation, renal samples were taken for the determination of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) levels and histological evaluation. The level of urea was measured in serum samples. RESULTS: Ischemia reperfusion significantly increased urea, and MDA levels, and decreased CAT and SOD activities. Histopathological findings of the IR group confirmed that there was renal impairment in the tubular epithelium. Treatment with EPO and MEL markedly decreased urea level and increased SOD and GPx activities. CONCLUSION: Treatment with EPO and MEL had a beneficial effect on renal IR injury. These results may show that the co-administration of MEL and EPO cannot exert more beneficial effects than either agent alone.