RESUMEN
Vitamin E is the generic term for a group of tocopherols and tocotrienols (T3). Hyperlipidemia has been known to cause progressive chronic renal dysfunction (CRD). Several investigators have reported that T3 have hypolipidemic and nephroprotective activity against free radical-related diseases. This study was conducted to determine if T3 as tocotrienol-rich fraction (TRF) from palm oil would protect against lipid-induced CRD in rats. For the induction of atherosclerosis and hyperlipidemia, Wistar male rats were fed an atherogenic diet containing 1.25% cholesterol, 0.5% cholic acid and 21% beef tallow (42.6% calories from fat). The atherogenic diet was given for 14 weeks to induce atherosclerosis. The control rats were given normal rat chow and drug control animals treated with TRF (100 mg/kg bw; orally). The first group was taken as disease control in which the animals were left untreated and given normal rat chow for six weeks, while the second group was treated with 100 mg TRF/kg bw. Atherosclerosis and renal functions were evaluated after six weeks of TRF treatment. Feeding an atherogenic diet to rats for 14 weeks resulted in dyslipidemia and impaired renal functions with decreased glomerular filtration rate. The treatment with TRF significantly reduced dyslipidemia and inhibited the development of CRD caused by atherogenic factors. These findings show that low-dose treatment of TRF may provide significant health benefits in the prevention of lipid-induced CRD. The study suggests that TRF is effective in preventing lipid-induced CRD.
Asunto(s)
Aterosclerosis , Hiperlipidemias , Aceites de Plantas/farmacología , Tocotrienoles/farmacología , Animales , Antioxidantes/farmacología , Aterosclerosis/complicaciones , Aterosclerosis/metabolismo , Dieta Aterogénica/métodos , Grasas Insaturadas en la Dieta/farmacología , Modelos Animales de Enfermedad , Radicales Libres/metabolismo , Hiperlipidemias/complicaciones , Hiperlipidemias/metabolismo , Fallo Renal Crónico/etiología , Fallo Renal Crónico/prevención & control , Pruebas de Función Renal/métodos , Masculino , Aceite de Palma , Preparaciones de Plantas/farmacología , Sustancias Protectoras/farmacología , Ratas , Ratas Wistar , Resultado del TratamientoRESUMEN
Dyslipidemia is common in patients with diabetes mellitus (DM) and is considered a risk factor for the progression of diabetic nephropathy (DN). Hyperlipidemia and hyperglycemia act synergistically to induce renal injury. The present study was designed to investigate the protective effects of tocotrienols as tocotrienol-rich fraction (TRF) extracted from palm (PO) and rice bran oils (RBO) against lipid induced nephropathy in type-2 diabetic rats and its probable molecular mechanism. Male Wistar rats (175-200 g) were divided into four groups. The first group served as diabetic control, while the second and third groups received PO-TRF and RBO-TRF, respectively by gavage over a period of sixteen weeks post-induction of diabetes. The fourth group comprised of age-matched rats that served as normal control. The effects of TRF on serum lipid profile, oxidative stress markers, expression of TGF-ß, fibronectin and collagen type IV were analyzed in the kidney of diabetic rats. Treatment with PO-TRF and RBO-TRF significantly improved glycemic status, serum lipid profile and renal function in type-2 diabetic rats. In addition, TRF supplementation down-regulated the expression of TGF-ß, fibronectin and collagen type IV in the kidney of diabetic rats. Transforming growth factor-ß (TGF-ß) plays a critical role in progression of DN, but its modulation by tocotrienols in DN remains unexplored. TRF ameliorated lipid induced nephropathy in type-2 diabetes by its hypoglycemic, hypolipidemic and antioxidant activities as well as by modulation of TGF-ß to prevent increased expression of collagen type IV and fibrinogen. We finally propose a mechanism for the expression of molecular markers that are significant in the events leading to diabetic nephropathy and its modulation by tocotrienols/TRF.
Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Nefropatías Diabéticas/sangre , Regulación de la Expresión Génica , Lípidos/sangre , Tocotrienoles/uso terapéutico , Factor de Crecimiento Transformador beta/biosíntesis , Animales , Diabetes Mellitus Tipo 2/prevención & control , Nefropatías Diabéticas/prevención & control , Masculino , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/uso terapéutico , Sustancias Protectoras/aislamiento & purificación , Sustancias Protectoras/uso terapéutico , Distribución Aleatoria , Ratas , Ratas Wistar , Tocotrienoles/aislamiento & purificación , Factor de Crecimiento Transformador beta/antagonistas & inhibidoresRESUMEN
Diabetic nephropathy (DN) is a serious complication confronted by patients with diabetes. Available data indicate that the development of DN is linked to hyperglycemia. Tocotrienol rich fraction (TRF) from palm oil (PO) and rice bran oil (RBO) has been shown to lower the blood glucose level in patients and preclinical animal models. This study was designed to investigate if TRF from PO and RBO could improve the renal function in DN by the virtue of their hypoglycemic and antioxidant activities. Male Wistar rats having an average body weight (bw) 250g were divided into four groups of six each .The first group served as diabetic control [injected with 55mg/kg bw of streptozotocin (STZ), intraperitoneally], while the second and third group received PO-TRF and RBO-TRF, respectively, by gavage at a dose of 200mg/kg bw/day, over a period of 8 weeks post-induction of diabetes. The fourth group comprised of age-matched male Wistar rats that received single intraperitoneal injection of normal saline only and served as control. After 8 weeks of STZ injection and TRF treatment, 24h urine was collected and animals were sacrificed. Fasting blood glucose, glycosylated hemoglobin, biochemical markers of renal function and oxidative stress were evaluated in serum, urine and kidney tissue. The results show that treatment with PO-TRF as well as RBO-TRF significantly improved the glycemic status and renal function in type 1 diabetic rats but PO-TRF afforded greater efficiency at similar dose as compared to RBO-TRF. In conclusion, PO-TRF was found to be more effective hypoglycemic and nephroprotective agent in DN than RBO-TRF.
Asunto(s)
Diabetes Mellitus Tipo 1/complicaciones , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/prevención & control , Hiperglucemia/complicaciones , Riñón/efectos de los fármacos , Aceites de Plantas/química , Tocotrienoles/farmacología , Animales , Antioxidantes/farmacología , Glucemia/metabolismo , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Creatinina/metabolismo , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/metabolismo , Ayuno , Hemoglobina Glucada/metabolismo , Hipoglucemiantes/farmacología , Riñón/metabolismo , Riñón/patología , Riñón/fisiopatología , Masculino , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Aceite de Palma , Proteinuria/metabolismo , Ratas , Ratas Wistar , Aceite de Salvado de ArrozRESUMEN
Industrial and occupational exposure to chromium compounds, particularly hexavalent chromium (Cr(VI))-containing compounds are often known to cause acute renal injury (ARI) in humans and animals. Its nephrotoxicity is associated with an increased formation of reactive oxygen species and lipid peroxidation in renal tissue. Recent studies suggest that antioxidants of the vitamin E family have protective effects against metal toxicity. Tocotrienols are known to have greater antioxidant activity than tocopherols and protect more efficiently against some free radical-related diseases than does tocopherols. In the present study, ARI induced by potassium dichromate (K(2)Cr(2)O(7)) has been used as a model to investigate the possible nephroprotective effect of tocotrienol-rich fraction (TRF) from palm oil. Wistar male rats having an average body weight (bw) of 210 g were divided into four groups. The first group was taken as control and injected with vehicle alone while the second group was drug control and ingested with TRF (200mg/kg, bw, orally, once daily for 21 days); the third group served as toxicant and was pre-treated with saline, followed by a single subcutaneous (SC) injection of K(2)Cr(2)O(7) (15 mg/kg bw). The fourth group was pre-treated with TRF and subsequently injected with K(2)Cr(2)O(7) (same dose as for the third group). Renal functions, oxidative and nitrosative stress were evaluated on days 0, 1, 2, 4, 7, 11 and 14 after treatment with K(2)Cr(2)O(7). The results revealed altered proximal tubular function; decreased glomerular filtration accompanied by oxidative damage 48 h after exposure to dichromate; while in the TRF-treated group proximal reabsorptive function, glomerular function and the cellular redox status were sustained. These results were further supported and confirmed by histological findings. The study suggests that TRF is effective in preventing K(2)Cr(2)O(7)-induced acute renal injury, but more studies are needed to confirm the effects of TRF as a nephroprotective agent.