Depletion of hepatic glutathione and adenosine by glucocorticoid exposure in Wistar rats is pregnancy-independent.

Liver diseases have gained increasing attention due to their substantial impact on health, independently as well as in association with cardio-metabolic disorders. Studies have suggested that glutathione and adenosine assist in providing protection against oxidative stress and inflammation while glucocorticoid (GC) therapy has been associated with chronic inflammatory disorders, even in pregnancy. The implications of Glucocorticoid exposure on maternal health and fetal growth is a concern, however, the possible role of glutathione and adenosine has not been thoroughly investigated. The study therefore hypothesize that exposure to glucocorticoids leads to depletion of hepatic glutathione and adenosine levels, contributing to oxidative stress and tissue injury. Additionally, we aim to investigate whether the effects of glucocorticoids on hepatic health are pregnancy dependent in female rats. Twelve Pregnant and twelve age-matched non-pregnant rats were used for this study; an exogenous administration of glucocorticoid (Dex: 0.2 mg/kg) or vehicle (po) was administered to six pregnant and six non-pregnant rats from gestational day 14 to 19 or for a period of 6 days respectively. Data obtained showed that GC exposure led to a decrease in hepatic glucose-6-phosphate dehydrogenase, glutathione peroxidase, GSH/GSSG ratio and adenosine content in both pregnant and non-pregnant rats. In addition, increased activities of adenosine deaminase and xanthine oxidase, along with increased production of uric acid and increased levels of lactate dehydrogenase, aspartate aminotransferase, alanine transferase, alkaline phosphatase and gamma-glutamyl transferase were observed. In summary, the study indicates that GC-induced liver damage is underlined by depleted hepatic adenosine and glutathione levels as well as elevated markers of tissue inflammation and/or injury. Furthermore, the findings suggest that the effects of GC exposure on hepatic health are pregnancy independent.

Chemical characterization, anti-nociceptive and anti-inflammatory activities of Plukenetia conophora seed oil in experimental rodent models.

ETHNOPHARMACOLOGICAL RELEVANCE: The seed of the African walnut, Plukenetia conophora Mull.-Arg is well-known for its nutritional and medicinal values. The seed oil is widely used in massages to relieve pain, as nerve tonic and to enhance sexual performance. OBJECTIVE: The study aimed at investigating the chemical profile, antinociceptive and anti-inflammatory activities of P. conophora oil (PCO). METHODS: Seed oil of P. conophora was characterized using Gas-Liquid Chromatographic method (GC-MS) and oral acute toxicity evaluated at 2000 mg/kg. Antinociceptive effects were evaluated in hot plate, acetic acid and formalin-induced paw licking tests. The anti-inflammatory effects were investigated in egg albumin and carrageenan-, formalin and complete Freund adjuvant (CFA)-induced paw oedema models. The levels of pro-inflammatory cytokines in the fluid exudates were also evaluated in carrageenan air pouch model. RESULTS: PCO exhibited high content of alpha linolenic acid (ALA). No toxicity was observed at 2000 mg/kg of PCO. PCO (50-200 mg/kg) demonstrated significant anti-nociceptive activity in pain models. PCO exhibited anti-inflammatory activity against oedema formation by phlogistic agents. The increased inflammatory oedema and oxidative stress in CFA-treated rats were also attenuated by PCO. The PCO (100 and 200 mg/kg) significantly reduced the levels of TNF-α (59.3% and 85.2%) and IL-6 (27.5% and 72.5%) in carrageenan-induced air pouch model. CONCLUSION: The results of this study suggest that ALA-rich seed oil of Plukenetia conophora demonstrated anti-nociceptive and anti-inflammatory activities via inhibition of pro-inflammatory cytokines and oxidative stress, lending supportive evidences for its use in painful inflammatory conditions.

Comparative Therapeutic Effect of Single/Combined Administration of Saxagliptin, Metformin and Intranasal Insulin on Dexamethasone Induced Insulin Resistance in Albino Wistar Rat Model.

Glucocorticoids have therapeutic benefits in the management of several inflammatory and immunological disorders. Despite these medicinal effects, they have the drawback of causing metabolic disorders such as hyperglycemia, insulin resistance etc., which is known to be a key indicator of metabolic syndrome. Metabolic syndrome is a major predisposing factor to type 2 diabetes mellitus and cardiomyopathy. This study was designed to compare and evaluate the effects of saxagliptin, metformin and intranasal insulin (when used singly or in combination) on dexamethasone induced insulin resistance. Fifty-six female rats were randomly assigned into eight groups. Group 1 represented the control; Group 2 was administered with dexamethasone (1mg/kg) (untreated); Group 3 received dexamethasone + intranasal insulin (2IU); Group 4 received dexamethasone + intranasal insulin + metformin (40mg/kg); Group 5; received dexamethasone + intranasal + saxagliptin (8mg/kg); Group 6 received dexamethasone + metformin (40mg/kg); Group 7 received dexamethasone + saxagliptin (8mg/kg); Group 8 received dexamethasone + saxagliptin(8mg/kg) + metformin(40mg/kg). Treatments were given for one week. At the end of the study, blood samples were collected for biochemical assays and pancreas excised for histological examination. Dexamethasone (1mg/kg) induced hyperglycemia, hyperinsulinemia, dyslipidemia, impaired glucose tolerance and disrupted the structural integrity of the pancreas. Treatment with saxagliptin, metformin and their combination significantly decreased blood glucose level, decreased LDL Level and improved glucose tolerance. The selected hypoglycemic agents used in present study ameliorate the dexamethasone induced hyperglycemia and insulin resistance of which the combination of metformin with saxagliptin showed greater efficacy.

A novel gedunin-2-hydroxypropyl-ß-cyclodextrin inclusion complex improves anti-nociceptive and anti-inflammatory activities of gedunin in rodents.

Gedunin is a bioactive compound, obtained from Entandrophragma angolense (EA), which has limited therapeutic usefulness due to poor aqueous solubility and first-pass effects. Cyclodextrins are cyclic oligosaccharides that form complexes with poorly soluble compounds, thus enhancing their pharmacological activity. In this article, we evaluated the pharmacological activities of gedunin-2-hydroxypropyl-ß-cyclodextrin complex (GCD) in rodents. The antinociceptive activity of GCD (50, 100, 200 mg/kg) and Gedunin (50mg/kg) was tested in acetic acid-induced writhing and formalin-induced paw licking in mice. The anti-inflammatory activity was investigated in carrageenan-induced paw oedema and air pouch inflammation models in rats. Leucocytes counts, Tumour Necrosis Factor-alpha (TNF-α) level, nitric oxide, malondialdehyde, reduced glutathione, and myeloperoxidase enzyme activities were assessed in the air pouch exudate. The GCD (200mg/kg) significantly decreased writhing response, reduced licking duration and decreased oedema compared with gedunin and control. Exudate volume and leucocyte count were significantly reduced by GCD (200 mg/kg), it decreased myeloperoxidase activity and inhibited TNF-α release. The carrageenan-induced GSH depletion, increased malondialdehyde and nitrite levels were significantly reversed by GCD (200 mg/kg) relative to gedunin and control.  The GCD complex demonstrated significant antinociceptive and anti-inflammatory activities relative to gedunin alone via mechanisms associated with inhibition of oxidative stress and inflammation in rodents.

Evaluation of acrylamide exposure in pregnant Wistar rats as a risk of developing renal disease in their litters.

This study was designed at evaluating the acrylamide (ACR) exposure in pregnant Wistar rats as a risk of developing renal disease in their litters. Four groups of pregnant female rats were used. Group 1 control animals were given 2 ml/kg/day of distilled water. Groups 2, 3, and 4 animals were given oral gavage doses of 2, 5, and 10 mg/kg/day of ACR respectively immediately pregnancy was confirmed. Mother rats were sacrificed 10 weeks after delivery and litters were sacrificed at 13 weeks. Proteinuria was observed in ACR-treated mother rats and their litters. Serum electrolytes, urea, and creatinine values observed in the treated group were deranged for both the mothers and litters respectively. Disruption of nephrogenesis was observed in the litters of ACR-treated mother compared to the control. The results of the effect of ACR on lipid profile indicated a significant elevation in the LDL, cholesterol, and triglyceride compared to the control. There was significant reduction in the SOD, catalase, GSH, and significant elevation in the C-reactive protein and malondialdehyde. Conclusively, exposure to acrylamide during pregnancy is a risk factor for the development of renal disease in the mother rats and their litters.

Neuroprotective and memory-enhancing effects of methanolic leaf extract of Peristrophe bicalyculata in rat model of type 2 diabetes mellitus.

This study investigated the effect of methanolic leaf extract of Peristrophe Bicalyculata (MEPb) on type 2 diabetes mellitus (T2DM) associated cognitive decline in Wistar rats. 36 male rats weighing 130-200 g were assigned into 6 groups (n = 6) as follows: normal control, diabetic control, pioglitazone-treated diabetic and three MEPb-treated diabetic groups, type 2 diabetes mellitus was induced with low dose streptozocin (STZ) injection following 3 weeks of high fat diet (HFD) intake. Thirty days after diabetes induction, rats exhibited marked and persistent hyperglycemia, animals were treated with MEPb (50, 100 and 200 mg/kg) and pioglitazone (10 mg/kg) as standard. Morris water maze (MWM) test and Novel object recognition test (NORT) were used to assess learning and memory. Blood glucose level, oxidative stress makers, pro-inflammatory marker and acetylcholinestarase activities were analysed. Both MEPb and pioglitazone significantly (P < 0.05) reduced escape latency in treated animals compared to the diabetic control group in the MWM test. Methanolic leaf extract of Peristrophe bicalyculata and pioglitazone also significantly (P < 0.05) increased discrimination index in treated animals compared to the diabetic control group in the novel object recognition test. Serum, brain and liver MDA levels were significantly (P < 0.05) decreased in MEPb and pioglitazone treated rats compared to diabetic control. Serum and liver GSH as well as CAT levels were significantly (P < 0.05) increased while brain GSH and CAT levels shows apparent increase in MEPb and pioglitazone treated rats compared with diabetic control. Treatment with MEPb caused a significant (P < 0.05) decrease in brain nitrite level, interleukin 6 and acetylcholinesterase activity compared to diabetic control group. We conclude that Methanolic leaf extract of Peristrophe bicalyculata enhanced antioxidant capacity and prevented neuroinflammation, consequently improving brain neuronal cholinergic function in experimental animals.

Subchronic exposure to Kafura; its neurotoxic potentials in young adult female Wistar rats.

BACKGROUND: Kafura pelebe (camphor) {C10H16O} is a chemical substance used mostly amongst the Yoruba ethnic group in Western Nigeria to treat infantile colic during early childhood. This study assess the neurotoxic potentials of Kafura following sub-chronic exposure in female albino Wistar rats. METHODS: Twenty-eight female rats (mean weight of 130 g) were randomly selected and assigned into four (4) groups. Control, received 1ml coconut oil while the treatment groups received 79, 158 and 237. mg/kg b.wt (d ose p.o) of Kafura for the period of 14 days. On day fifteen, animals were dissected and the brain organ excised for the homogenate and histopathologic assay, blood samples were also collected for haematological analysis. Morris Water Maze experiment for reference memory was also carried out to ascertain effect of Kafura in the Central Nervous system (CNS). RESULTS: A trend toward decreased body-weight gain and increase brain weight was observed in Kafura-treated rats but was statistically not significant, compared to control. The biochemical assessment of the antioxidant status of brains of Kafura-treated rats showed significant (p ≤ 0.05) increase in activities of some anti-oxidant enzymes (Superoxide dismutase (SOD), Glutathione peroxide (GPx), and Catalase (CAT)). There was increase in acetylcholinesterase (AChE), Malondialdehyde (MDA), and Total protein activities in the brain of treated rats compared to control. Alterations of the haematological parameters were observed, with the plasma granulocytes, lymphocytes, and haemoglobin (HGB), showing significant decrease in the treated rats compared to control. The water maze test showed a marked increase in spatial learning and memory time (seconds) in kafura-treated rats, compared to control and across treated groups. CONCLUSIONS: The present study provides indication that kafura Pelebe shows apparent neurotoxicity in experimental animals. Incessant exposure in humans though may lead to development of some central nervous system defects.

Ocimum gratissimum Linn. Leaf extract inhibits free radical generation and suppressed inflammation in carrageenan-induced inflammation models in rats.

BACKGROUND: Ocimum gratissimum leaf is used in managing rheumatism and other inflammatory conditions. In this study, we investigated the antioxidant and anti-inflammatory effects of phenolic extract obtained by sequential methanol extraction of O. gratissimum leaves (MEOg). METHODS: The methanol extract (MEOg) was obtained after sequential maceration (n-hexane, chloroform and methanol) of dried O. gratissimum leaves. The fingerprint of the extract was obtained using a high-performance liquid chromatrographic method. In vitro effects were tested by 1,1-Diphenyl-2-picryl-hydrazyl (DPPH), nitric oxide (NO) free radical scavenging, lipoxygenase, and xanthine oxidase inhibitory assays. MEOg was studied for anti-inflammatory activity in carrageenan-induced paw edema and air pouch inflammation in rats. RESULTS: HPLC fingerprint of the extract shows the presence of caffeic acid, rutin, ferulic acid, apigenin, and quercetin. Antioxidant activity of MEOg revealed an IC50 value in DPPH (31.5±0.03 µg/mL) and NO assay (201.6±0.01 µg/mL), respectively. The extract demonstrated strong xanthine oxidase inhibitory and weak antilipoxygenase activities. MEOg (100 mg/kg) significantly inhibited carrageenan-induced paw edema by 43.2%. Furthermore, MEOg (50 and 100 mg/kg) significantly reduced exudate volume, leucocyte count, neutrophil infiltration, TNF-α, nitrites, myeloperoxidase, and malondialdehyde in carrageenan-induced air pouch inflammation. MEOg also elevated the glutathione levels in the inflammatory exudates. CONCLUSIONS: MEOg shows potential therapeutic benefits in slowing down inflammation and oxidative stress in chronic diseases, such as arthritis.