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1.
PLoS One ; 19(4): e0301992, 2024.
Article En | MEDLINE | ID: mdl-38640098

BACKGROUND AND OBJECTIVE: Diabetic neuropathy (DN) is a complex type of diabetes. The underlying cause of diabetic nephropathy remains unclear and may be due to a variety of pathological conditions resulting in kidney failure. This study examines the protective effect of the methanolic extract of Spilanthes filicaulis leaves (MESFL) in fructose-fed streptozotocin (STZ)-induced diabetic nephropathy and the associated pathway. METHODS: Twenty-five rats were equally divided randomly into five categories: Control (C), diabetic control, diabetic + metformin (100 mg/kg), diabetic + MESFL 150 mg/kg bw, and diabetic + MESFL 300 mg/kg bw. After 15 days, the rats were evaluated for fasting blood glucose (FBG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea, uric acid, serum creatinine, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (MDA). Gene expression levels of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response element-binding (CREB), cFOS and the antiapoptotic protein Bcl-2 were examined. RESULTS: We observed that MESFL at 150 and 300 mg/kg bw significantly downregulated the protein expression of cAMP, PKA, CREB, and cFOS and upregulated the Bcl-2 gene, suggesting that the nephroprotective action of MESFL is due to the suppression of the cAMP/PKA/CREB/cFOS signaling pathway. In addition, MESFL increases SOD and CAT activities and GSH levels, reduces MDA levels, and reduces renal functional indices (ALP, urea, uric acid, and creatinine). CONCLUSION: Therefore, our results indicate that MESFL alleviates the development of diabetic nephropathy via suppression of the cAMP/PKA/CREB/cFOS pathways.


Diabetes Mellitus , Diabetic Nephropathies , Rats , Animals , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/prevention & control , Diabetic Nephropathies/metabolism , Streptozocin/pharmacology , Kidney/pathology , Uric Acid/metabolism , Superoxide Dismutase/metabolism , Oxidative Stress , Diabetes Mellitus/pathology
2.
Toxicol Rep ; 5: 324-332, 2018.
Article En | MEDLINE | ID: mdl-29854601

Exposure to cadmium (Cd), even at low doses, is of serious health concern because it does not undergo metabolic degradation to less toxic metabolite. Liver injury/disease, with a world-wide increasing incidence, is one of the consequences of exposure to Cd toxicity. This study aimed at determining the effects of acetonic extract of Vernonia amygdalina leaf (AEVAL) in a Wistar rat model of Cd-induced liver injury. Phytochemical screening of the extract was carried out and its oral LD50 was determined to guide the choice of therapeutic doses. Thereafter, thirty male Wistar rats were recruited for this study. The experimental groups received 4 weeks oral graded doses of the extract (100, 200 and 400 mg/kg) following Cd-induced liver injury. Cd-induced liver injury (5 mg/kg i.p for 5 consecutive days) was characterized by deleterious alterations in the levels of AST, ALT, ALP, total bilirubin and hepatic total protein (p ˂ 0.05). Also, deleterious alteration of oxidative stress indicators (GSH, SOD and CAT) and lipid peroxidation index (TBARS) was observed in the liver homogenates. Histopathological examination showed evidence of degenerated hepatocytes as well as inflammation with disseminated steatosis. These conditions were significantly attenuated (p ˂ 0.05) following treatment with graded doses of the extract, with the highest dose expressing least therapeutic effects. This study concluded that AEVAL attenuated Cd-induced liver injury and is, potentially, a suitable option in adjuvant therapy for heavy metal toxicity.

3.
J Am Coll Nutr ; 37(5): 387-398, 2018 07.
Article En | MEDLINE | ID: mdl-29425480

OBJECTIVES: Cisplatin (CIS) is an effective antitumor drug. However, its clinical use is limited due to nephrotoxicity. l-Carnitine and vitamin C are both natural antioxidant that can be obtained from diets. This study investigated the effects of l-carnitine and/or vitamin C in rats against cisplatin-induced nephrotoxicity. METHODS: Twenty-five male Wistar rats were divided into 5 groups of 5 rats each. Group 1, normal control. Group 2, positive control, received cisplatin (10 mg/kg/day intraperitoneally [i.p.]) for 3 days. Groups 3, 4, and 5 received cisplatin for 3 days and thereafter l-carnitine (50 mg/kg/day), vitamin C (100 mg/kg/day), or their combination, respectively, for 28 days. At the end of the study, a biochemical study was carried out in which nephrotoxicity markers, electrolytes, hematological indices, oxidative stress biomarkers, and renal histopathological alterations were evaluated. RESULTS: CIS-treated rats developed significant polyuria, increase in the plasma levels of creatinine, urea, and inorganic phosphate (Pi), alteration in hematological parameters, and decrease in plasma levels of Na+, Cl-, K+, Ca2+, and Mg2+. Measurements of 24-hour urine output demonstrated markedly decreased creatinine and urea and increased Na+, Cl-, K+, Ca2+, and Mg2+ levels in the CIS-treated group, whereas Pi levels were not changed. It also caused significantly decreased catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) levels in the rats' kidneys. Histopathological scores revealed renal tubular damage in CIS-treated rats. However, l-carnitine, vitamin C, or their combination significantly attenuated the alterations caused by CIS in the plasma and kidneys of the rats. CONCLUSION: l-Carnitine and vitamin C administration ameliorated CIS-induced nephrotoxicity due to their antioxidant and anti-inflammatory effects.


Antioxidants/pharmacology , Ascorbic Acid/pharmacology , Carnitine/pharmacology , Cisplatin/toxicity , Kidney/drug effects , Acute Kidney Injury/chemically induced , Acute Kidney Injury/physiopathology , Animals , Biomarkers/blood , Biomarkers/urine , Body Weight/drug effects , Creatinine/blood , Creatinine/urine , Electrolytes/blood , Electrolytes/urine , Kidney/pathology , Kidney/physiopathology , Male , Oxidative Stress/drug effects , Rats , Rats, Wistar , Urea/blood , Urea/urine
4.
Animal Model Exp Med ; 1(4): 295-304, 2018 Dec.
Article En | MEDLINE | ID: mdl-30891579

BACKGROUND: The study determined the fractions of proteins in the urine and plasma of rats at different ages, measured the plasma and urine concentrations of markers of renal function, with a view to determining the influence of proteinuria on renal function. METHODS: Eighty Wistar rats were used for this study. Groups 1 and 2 each consisted of eight 1-month-old male and female rats; 3 and 4 had eight 3-month-old male and female rats; 5 and 6 had eight 6-month-old male and female rats; 7 and 8 had eight 9-month old male and female rats; and 9 and 10 had eight 12-month-old male and female rats. RESULTS: A fraction of the molecular weight of protein in the urine of rats aged 1, 9 and 12 months was higher than that of 3 and 6 months. The total protein concentration in the urine of male and female rats aged 9 and 12 months was significantly higher than that of rats aged 1 and 3 months. The urine creatinine concentrations of male and female rats aged 9 months were significantly higher when compared with that of 1, 3, 6 and 12 months. CONCLUSION: Our results suggest that the 3-month-old rats seem less affected by proteinuria, because they had the least urine protein, and consistent and reduced plasma and urine concentrations of markers of renal function. The results of this study may provide a foundation for future mechanistic inquiries as to why this age group was the least affected by proteinuria.

5.
J Diet Suppl ; 15(5): 649-664, 2018 Sep 03.
Article En | MEDLINE | ID: mdl-29087735

Nauclea latifolia is used in traditional medicine for the treatment of male reproductive diseases. Despite its vast uses, its effects on the male reproductive system have not been scientifically proven. This study aimed to investigate the effects of Nauclea latifolia root decoction on sexual behavior and functions in male rabbits. Twenty-four male rabbits were divided into four groups: The first group received daily distilled water orally. The second, third, and fourth groups were orally treated with 100, 200, and 400 mg/kg body weight of Nuclea latifolia root, respectively. Sexual behavior parameters were carried out on weeks 1, 2, and 3 of the study. Testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured from the serum, while the testes tissue samples were used for antioxidant and histopathological examinations. Treatment with 200 and 400 mg/kg body weight resulted in significantly (p < .05) increased frequencies of mounting and intromission. In addition, the ejaculation latency was significantly prolonged (p < .05). The latencies of mounting and intromission were significantly decreased (p < .05), whereas ejaculation frequency increased. Serum testosterone, FSH, and LH increased significantly (p < .05) after treatment with Nuclea latifolia. There was an increase in epididymal sperm counts at 200 and 400 mg/kg body weight doses compared to the control. The extract also increased sperm motility and viability and improved testicular oxidative status. Histological examination revealed an increase in germinal layer thickness. The present study suggests that treatment with N. latifolia improves male sexual function and fertility and protects the testes from oxidative damage.


Plant Extracts/pharmacology , Plant Roots/chemistry , Reproduction/drug effects , Rubiaceae , Sexual Behavior, Animal/drug effects , Animals , Antioxidants , Ejaculation/drug effects , Female , Fertility/drug effects , Follicle Stimulating Hormone/blood , Litter Size/drug effects , Luteinizing Hormone/blood , Male , Phytotherapy , Plant Extracts/analysis , Rabbits , Spermatozoa/drug effects , Testis/anatomy & histology , Testis/chemistry , Testosterone/blood
6.
Pathophysiology ; 24(4): 281-290, 2017 Dec.
Article En | MEDLINE | ID: mdl-28822616

This study sought to investigate the effects of kolaviron on diclofenac-induced hepatotoxicity in rats. Sixty male Wistar rats were divided into 6 groups of 10 rats each as follows: a control group that received oral propylene glycol and treatment groups that received diclofenac alone, diclofenac followed by Livolin Forte (a reference drug), or diclofenac followed by kolaviron at three different doses. At the end of the study period, five rats per group were sacrificed under ketamine hydrochloride anesthetic, 24h after treatment, while the other 5 rats in the group were allowed to recover for 2 weeks before being sacrificed. Liver enzyme activities, total bilirubin levels, and the concentrations of several pro-inflammatory cytokines were determined using plasma samples, while liver tissue samples were used for antioxidant analysis and histopathological examination. Compared with the control group, plasma liver enzyme activities, along with bilirubin levels, were higher in the groups that received diclofenac alone or diclofenac+the highest dose of kolaviron, respectively. These groups had higher plasma concentrations of pro-inflammatory cytokines than did the control group. However, the administration of Livolin Forte and kolaviron (at the lower doses) ameliorated diclofenac-induced hepatic injury by improving antioxidant status, preventing an increase in inflammatory mediators, decreasing malondialdehyde, and attenuating the adverse effect of diclofenac on hepatic tissues. In addition, there was a significant difference in the histological scores between the groups that received either diclofenac alone or diclofenac followed by the highest dose of kolaviron when compared with the other three groups (Livolin Forte or lower doses of kolaviron). In conclusion, kolaviron appears to be as effective as Livolin in attenuating DCLF-induced hepatotoxicity in rats. However, high doses of kolaviron seem to cause damage to the liver.

7.
Toxicol Rep ; 4: 535-542, 2017.
Article En | MEDLINE | ID: mdl-29657920

The adverse and beneficial health effects of nicotine (NIC), the major alkaloid found in cigarettes and tobacco, are controversial. Most studies on NIC have focused on its effects on cardiovascular and nervous functions. This study aimed at determining dose- and sex-specific effects of sub-acute (28 days) NIC administration on some indices of kidney function in Wistar rats. Forty rats (20 males and 20 females), 8-9 weeks old (each housed in separate metabolic cage), were used for this study such that graded doses of NIC (1, 2 and 4 mg/kg i.p. for 28 days) were administered to both sexes while each control received distilled water at 0.2 mL/100 g i.p. Blood was collected under ketamine anesthesia (10 mg/kg i.m) for analyses and results obtained were compared at p < 0.05. The result showed beneficial alterations in plasma and urine level of creatinine, urea and uric acid (p < 0.05) as well as plasma and urine electrolyte level (Na+ and K+) in both sexes (p < 0.05). Also, there was significant improvement in creatinine clearance (p < 0.05) with no appreciable difference in their histological examination. Although these beneficial effects were more pronounced in the female than in the male (p < 0.05), administration at the highest dose showed potentially deleterious alterations from normal beneficial trend (p < 0.05) in both sexes. It was concluded that sub-acute administration of lower doses of NIC improves kidney function of Wistar rats; an effect that was more pronounced in the females than their male counterparts.

8.
J Intercult Ethnopharmacol ; 4(4): 284-92, 2015.
Article En | MEDLINE | ID: mdl-26649233

AIM: To determine the effects of polyphenol-rich extract of the leaves of Vernonia amygdalina (PEVA) on the feeding pattern of rats that were exposed to cadmium (Cd) toxicity. MATERIALS AND METHODS: Thirty male Wistar rats, weighing 160-180 g, were divided into 6 groups of 5 rats each as follows; Group 1 received distilled water orally (0.2 ml/100 g), daily, throughout the period of study. Group 2 received Cd alone (in the form of CdSO4) at 5 mg/kg/day via intraperitoneal route for 5 consecutive days. Group 3 were pre-treated with Cd as Group 2 and thereafter left untreated for a period of 4-week. After the oral lethal dose of PEVA was determined, Groups 4, 5, and 6 were pre-treated with Cd as Group 2 after which they received graded doses of PEVA at 100, 200 and 400 mg/kg/day (0.2 ml/100 g), respectively via oral route for 4 weeks. Blood samples were collected for some plasma biochemical assays while urine samples were collected using metabolic cages. RESULTS: PEVA administration significantly increased (P < 0.05) the body weight and feeding patterns that were significantly reduced (P < 0.05) by Cd toxicity. PEVA also significantly reinstated the plasma antioxidant status, as well as glucose and urine volume of the rats toward control values (P < 0.05). CONCLUSION: PEVA can be an herbal alternative in the treatment or management of subjects manifesting alterations in feeding pattern and urine volume that is Cd-induced.

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