Background: Cisplatin is frequently used as an anticancer medication. Nephrotoxicity and hepatotoxicity are triggered by its usage, causing patients to limit their long-term therapy. Aim: To investigate the underlying mechanism of omega-3 (fatty acids) effect on hepatorenal toxicity induced by cisplatin in rats and to detect whether it has a protective or therapeutic effect or both and the role of HO-1 enzyme in both effects. Materials and Methods: 40 male rats were divided into four equal groups: Control group: received i.p. saline+ corn oil orally, Cisplatin Group: received i.p. CP (12 mg/kg)+ corn oil orally, Cisplatin+ ω-3 pretreatment group: received i.p. CP following 10 days of ω-3 pretreatment in dose {(270 mg/kg) EPA, (180 mg/kg)} and Cisplatin+ ω-3 post-treatment group: received i.p. CP followed by 10 days of ω-3 post-treatment in dose as the previous group. Liver and kidney function, serum (HO-1), serum& tissue (TNF-α, IL-10), tissue (NFkB, GSH, MDA), and NrF2 gene expressions were measured. Results: Cisplatin-induced marked hepatorenal failure; detected by elevation of serum: AST, ALT, creatinine, and urea. Also, serum& tissue (TNF-α, IL-10), and tissue (NFkB, GSH, MDA) were significantly changed with no change in NrF2 gene expressions as compared to the control. On other hand, pre or post-ω-3 intake significantly corrected the changed markers. Liver and renal histopathological and immunohistochemical changes confirmed the biochemical results in all groups. Conclusion: Cisplatin treatment impairs liver and kidney function, while ω-3 supplementation could avoid this toxicity, with the protective response appearing to be more beneficial than the therapeutic effect.

Growing evidence supports the role of the gut-kidney axis and persistent mitochondrial dysfunction in the pathogenesis of diabetic nephropathy (DN). Ulinastatin (UTI) has a potent anti-inflammatory effect, protecting the kidney and the gut barrier in sepsis, but its effect on DN has yet to be investigated. This study aimed to assess the potential mitigating effect of UTI on DN and investigate the possible involvement of gut-kidney axis and mitochondrial homeostasis in this effect. Forty male Wistar rats were divided equally into four groups: normal; UTI-treated control; untreated DN; and UTI-treated DN. At the end of the experiment, UTI ameliorated DN by modulating the gut-kidney axis as it improved serum and urinary creatinine, urine volume, creatinine clearance, blood urea nitrogen, urinary albumin, intestinal morphology including villus height, crypt depth, and number of goblet cells, with upregulating the expression of intestinal tight-junction protein claudin-1, and counteracting kidney changes as indicated by significantly decreasing glomerular tuft area and periglomerular and peritubular collagen deposition. In addition, it significantly reduced intestinal and renal nuclear factor kappa B (NF-κB), serum Complement 5a (C5a), renal monocyte chemoattractant protein-1 (MCP-1), renal intercellular adhesion molecule 1 (ICAM1), and renal signal transducer and activator of transcription 3 (STAT3), mitochondrial dynamin related protein 1 (Drp1), mitochondrial fission 1 protein (FIS1), mitochondrial reactive oxygen species (ROS), renal hydrogen peroxide (H2O2), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. Furthermore, it significantly increased serum short chain fatty acids (SCFAs), and mitochondrial ATP levels and mitochondrial transmembrane potential. Moreover, there were significant correlations between measured markers of gut components of the gut-kidney axis and renal function tests in UTI-treated DN group. In conclusion, UTI has a promising therapeutic effect on DN by modulating the gut-kidney axis and improving renal mitochondrial dynamics and redox equilibrium.

We aimed to examine the link between fetuin A and different grades of obesity with its potential link to its complication and to determine the effect of exercise on its levels as well as on obesity complications. Methods: 40 male rats were classified based on adiposity index by using cluster analysis to 4 groups: G1: normal weight with no physical training n=10, G2: Overweight n=9, G3: Obese n=11 and G4: normal weight with physical training n=10. Albumin and creatinine were determined in urine and serum levels of fetuin-A, adiponectin, TNF-α, MDA, GSH, lipid profile and HOMA IR were measured. Also, liver NFkappa and renal relative AMPK mRNA expression were determined. Results: Fetuin-A, MDA, TNF-α, LDL, TG, HOMA IR, NFkappa, Adiposity index and ACR were significantly higher while adiponectin, GSH, HDL and relative AMPK mRNA expression were significantly lower in group2,3 as compared to group1,4 and as compared to each other. While, group3 showed significant increase in ACR, as compared to group1,2,4 but there was no significant change in ACR in group2. Group4 showed significant increase in adiponectin, GSH, HDL and relative AMPK mRNA expression and significant decrease in fetuin-A, TNF-α, MDA, HOMA IR, LDL ,TG, NFkappa, adiposity index and ACR as compared to group2,3. Also, positive correlation between fetuin-A and Adiposity index, ACR and NFkappa with negative correlation between it and adiponectin detected in group2,3,4.Conclusion: Fetuin-A level is directly proportional to obesity grades and its complication. Also, exercise appears to have protective role by decreasing fetuin-A level.