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1.
Toxicol Res (Camb) ; 10(6): 1092-1103, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34992771

RESUMO

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.

2.
J Pharm Pharmacol ; 72(11): 1615-1628, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32754951

RESUMO

OBJECTIVES: This study was designed to investigate the effect of Morus nigra fruit extract in retarding the progression of diabetic nephropathy in streptozotocin (STZ)-induced diabetic rats. METHODS: Diabetic male Wistar rats were injected with black mulberry fruit extract (BMFE) at doses of 150 and 300 mg/kg body weight. After 4 weeks, microalbuminuria was estimated in addition to serum concentrations of glucose, insulin, creatinine and albumin. KEY FINDINGS: The study revealed a significant amelioration of all the measured parameters in diabetic animals. In addition, MDA, lipid peroxide levels and catalase activity were also improved. The histopathological examination of kidney tissues revealed significant improvement of the pathological changes and glomerular sclerosis in diabetic rats treated with BMFE. Treated rats showed downregulation of TNF-α, vascular cell adhesion molecule-1 (VCAM-1) and fibronectin mRNA expression. CONCLUSION: The ameliorative effect of BMFE on diabetic nephropathy is not only through its potent antioxidant and hypoglycaemic effects but also through its downregulation of TNF-α, VCAM-1 and fibronectin mRNA expression in renal tissues of diabetic-treated rats. Therefore, BMFE as dietary supplement could be a promising agent in improving diabetic nephropathy.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Hipoglicemiantes/farmacologia , Rim/efeitos dos fármacos , Morus , Extratos Vegetais/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Albuminúria/etiologia , Albuminúria/metabolismo , Albuminúria/prevenção & controle , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Regulação para Baixo , Fibronectinas/genética , Fibronectinas/metabolismo , Frutas , Hipoglicemiantes/isolamento & purificação , Rim/metabolismo , Rim/patologia , Masculino , Morus/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Ratos Wistar , Transdução de Sinais , Estreptozocina , Fator de Necrose Tumoral alfa/genética , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo
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