ABSTRACT
One of the main antineoplastic chemotherapy medications is cisplatin, of which nephropathy is a major side effect. In this current study, we aim to investigate the molecular protective effect of Spirulina platensis (SP) on cisplatin-induced nephrotoxicity. In total, 48 healthy male albino rats were allocated into 4 groups. Group 1 received saline intraperitoneally (IP) twice per week (normal rats). Group 2 received SP (100 mg/kg BW orally). Group 3 were injected with cisplatin (1.5 mg/kg IP) twice per week. Group 4 received SP and on the 4th day received cisplatin (1.5 mg/kg IP) for 21 days. After 3 weeks of experiment, blood and renal tissues were taken for serum analysis, gene expression using qRT-polymerase chain reaction, and renal histopathology. As per our findings, it was found that SP significantly ameliorated the alterations in body weight, relative kidney weight, and the disturbance in examined renal markers. Furthermore, SP recovered and restored cisplatin-induced oxidative stress biomarkers (MDA and NO) and antioxidant activity (SOD and GSH) and cisplatin-induced upregulation in the gene expression of TNF-α, inducible nitric oxide synthase, TGF1-ß, IL-1ß, and IL-6. Interestingly, these gene expressions were ameliorated by the SP pre-administration. Furthermore, cisplatin upregulated pro-apoptotic gene Bax, whereas it downregulated anti-apoptotic gene Bcl2. Interestingly, SP mitigated this alteration in apoptosis and anti-apoptotic associated genes. Renal histopathology revealed the protective impacts of SP against cisplatin-induced severe glomerular congestion, hemorrhage, inflammatory cell infiltration, degeneration, and severe necrosis in renal glomeruli and tubules. In conclusion, SP has a protective effect against cisplatin-induced renal damage through modulating oxidative stress and anti-inflammatory, anti-necrotic, and anti-apoptotic-associated genes.
ABSTRACT
Hepatocellular carcinoma (HCC) is a serious threat to human health that has attracted substantial interest. The purpose of this study was to investigate the modulatory effect of bee honey against induced HCC by diethylnitrosamine/carbon tetrachloride (DEN/CCl4) in rats. HCC was induced by a single intraperitoneal dose of DEN (200 mg/kg B.W). Two weeks later, CCl4 (1 ml/kg) was intraperitoneally injected (three times a week). Bee honey was administered orally at 2 g/rat before and after the induction of HCC. The results showed that bee honey administration significantly increased body weight, decreased liver weight, and relative liver weight compared to those in the HCC-induced group. Moreover, a significant decrease in serum alpha-fetoprotein (AFP) as well as AST, ALT, GGT, ALP activities were observed in bee honey administration rats compared with those in HCC-induced group. Also, the hepatic MDA was significantly decreased; in addition, SOD, CAT, and GPx activities were significantly increased in groups treated with bee honey compared with those in the HCC group. The hepatic histopathology alterations caused by DEN/CCl4 injection were ameliorated by bee honey treatment. Likewise, the mRNA expression levels of tumor necrosis factor-alpha (TNF-α), transforming growth factor (TGF-ß1), intracellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), glypican (GP-3), thioredoxin (TRX), and glutaredoxin (GRX) were downregulated, and caspase-3 was upregulated by bee honey treatment compared with untreated HCC-induced group. In conclusion, bee honey has remarkable beneficial effects against HCC induced in rats through its antioxidant, anti-inflammatory, antifibrotic, and antimetastatic effects. PRACTICAL APPLICATIONS: The current study confirmed that honey has the potential to act as an antimetastatic factor. Bee honey supplementation either before or after combined injection of DEN/CCl4 exhibited inhibitory and ameliorative effects against DEN/CCl4-induced HCC through its antioxidant, antiproliferative, anti-metastatic, antifibrotic, and apoptosis properties. To our knowledge, this is the first study to describe the molecular mechanisms underlying honey's effects against DEN/CCl4-induced HCC in rats.
