Pharmacokinetics and clinical evaluations of gentamicin-induced nephrotoxicity in puppies

Background: The study was aimed at investigating the effect of dosing intervals on gentamicin nephrotoxicity in puppies.Methods: Local puppies were assigned to Groups A and B (n=6) and administered gentamicin intramuscularly once (6 mg/kg) or twice (3 mg/kg) daily, respectively, for 5 consecutive days. Biochemical parameters such as urine protein, creatinine, ɤ-glutamyl transferase, as well as serum creatinine (SCR) and urea nitrogen were determined spectrophotometrically using specific kits before and after treatment. Peak and trough serum concentrations of gentamicin were determined by immunoassay on 1st and 5th day treatment. Thereafter, elimination rate constants and corresponding half-lives were calculated.Results: No significant increase in SCR concentrations in both groups was observed, but values on day 7 were slightly above normal. Conversely, there was a significant increase above normal in serum urea nitrogen on days 4 and 7 in Group A, whereas this was observed only on day 7 in Group B. Even though all other biochemical parameters assayed for were within normal, an increasing trend was noticed as the length of treatment days increased in both groups. In both groups, peak serum concentrations of gentamicin did not differ significantly. There was a 4- and 16-fold significant increase in trough levels after the last treatment in Groups A and B, respectively. Although peak and trough concentrations increased with increasing length of treatment, all the values were well below 10 µg/ml and 2 µg/ml, respectively, as required.Conclusion: These suggest the risk of nephrotoxicity following treatment with gentamicin beyond 5 consecutive days irrespective of the dosing interval in puppies

A case of polydactyly in the hind-limbs of a West African Dwarf goat in South-West Nigeria

This report describes a case of polydactyly in the hind-limb of a West African Dwarf goat kid in South West Africa. Physical examination revealed the presence of four digits in each of the hind limbs. Radiological examination and macerated bones of the animal showed a bifid shape of each metatarsal that was more prominent from the distal half of the diaphysis. This resulted in the presence of four articulating surfaces per limb at the distal extremity. Though this condition is rare in goats, we advise that continuous reporting by researchers can give a better prevalence statistics of these occurrences

Antidiabetic and anti-oxidant activities of the methanol leaf extract of <i>Vernonia amygdalina</i> in alloxan-induced diabetes in Wistar rats

The methanolic leaf extract of Vernonia amygdalina (MLVA) was assessed to evaluate its antidiabetic potential in rats. Diabetes was induced in male Wistar rats by the administration of alloxan monohydrate at 100 mg/kg of body weight. After 48 h, rats with fasting blood glucose levels of 200 mg/dL and above were considered diabetic and used for the study. The experimental animals were grouped into five groups (A–E) of 10 animals each. Group A rats were non-diabetic normal control, Group B consisted of diabetic control rats that received no treatment, groups C, D and E rats were diabetic rats but treated with glibenclamide, 200 and 400 mg/kg doses of MLVA respectively. Blood samples were collected at days 14 and 28 after induction for haematological and serum biochemical indices such as triglycerides, LDL, cholesterols etc. The intestine was collected and intestinal homogenate was prepared for the antioxidant studies. The extract at 200 mg/kg and 400 mg/kg doses significantly (p < 0.05) reduced blood glucose levels in extract-treated diabetic rats and also significantly increased weight gain in these rats. Most haematological parameters in treated rats experienced, while platelets and neutrophils were decreased. Biochemical indices measured were reduced in MLVA-treated groups compared with diabetic control. Treatment with MLVA also produced significant (p < 0.05) decrease in markers of oxidative stress but increased levels of enzymic and non-enzymic antioxidant markers in intestinal homogenates of treated groups compared with diabetic control. This study showed that V. amygdalina has antihyperglycaemic and in vivo antioxidant effects

Cardioprotective effects and antioxidant status of Andrographis paniculata in isoproterenol-induced myocardial infarction in rats

Background: Myocardial infarction has been regarded as one of the fastest killer diseases of modern-day man. Aim: The protective effect of Andrographis paniculata on isoproterenol (ISO)-induced myocardial infarction in rats was investigated. Setting: The study was carried out in a laboratory setting. Methods: Animals were randomly divided into six groups of seven animals per group, and the treatment was as follows: normal control received normal saline for 9 days, isoproterenol group; three extract-treated groups in pre-treatment phase and an extract-treated group in post-treatment phase. The doses were given at 100, 200 and 400 mg/kg body weight for pre-treatment phase respectively while 200 mg/kg dose was given to the post-treatment phase group. Blood and heart tissues were collected for biochemical assays, haematological and histological analyses. Results: Myocardial infarction was recorded in ISO group but was corrected by the extracts in both pre-treatment and post-treatment phases. The ISO group experienced a significant decrease in antioxidant parameters, whereas the extract at all doses caused a significant increase in the activities of in these parameters. The extract caused a significant decrease in malondialdehyde content and hydrogen peroxide generation, whereas reverse was the case for the ISO group. Although no significant histopathological changes were recorded for the extract, the ISO group showed marked histopathological changes. ISO caused higher expressions of cardiac C-reactive protein (CRP) and CTnI and decreased the expressions of IL-10β; but this was the opposite for the extract. Conclusion: The ethanol leaf extract of A. paniculata significantly exhibits cardioprotective effects

Clofibrate, a peroxisome proliferator–activated receptor-alpha (PPARα) agonist, and Its molecular mechanisms of action against sodium fluoride–induced toxicity

AVAILABILITY OF DATA AND MATERIALS : Data will be made available based on request from the corresponding author.Sodium fluoride (NaF) is one of the neglected environmental pollutants. It is ubiquitously found in the soil, water, and environment. Interestingly, fluoride has been extensively utilized for prevention of dental caries and tartar formation, and may be added to mouthwash, mouth rinse, and toothpastes. This study is aimed at mitigating fluoride-induced hypertension and nephrotoxicity with clofibrate, a peroxisome proliferator–activated receptor-alpha (PPARα) agonist. For this study, forty male Wistar rats were used and randomly grouped into ten rats per group, control, sodium fluoride (NaF; 300 ppm) only, NaF plus clofibrate (250 mg/kg) and NaF plus lisinopril (10 mg/kg), respectively, for 7 days. The administration of NaF was by drinking water ad libitum, while clofibrate and lisinopril were administered by oral gavage. Administration of NaF induced hypertension, and was accompanied with exaggerated oxidative stress; depletion of antioxidant defence system; reduced nitric oxide production; increased systolic, diastolic and mean arterial pressure; activation of angiotensin-converting enzyme activity and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB); and testicular apoptosis. Treatment of rats with clofibrate reduced oxidative stress, improved antioxidant status, lowered high blood pressure through the inhibition of angiotensin-converting enzyme activity, mineralocorticoid receptor over-activation, and abrogated testicular apoptosis. Taken together, clofibrate could offer exceptional therapeutic benefit in mitigating toxicity associated with sodium fluoride.Cape Peninsula University of Technology and National Research Foundation (South Africa).https://link.springer.com/journal/12011hj2023Paraclinical Science

The methanol seed extract of Garcinia kola attenuated angiotensin II- and lipopolyssacharide-inducedvascular smooth muscle cell proliferation and nitric oxide production

All over the world, cardiovascular diseases are a risk factor for poor health and early death with predisposing factors to include age, gender, tobacco use, physical inactivity, excessive alcohol consumption, unhealthy diet, obesity, family history of cardiovascular disease, hypertension, diabetes mellitus, hyperlipidemia, psychosocial factors, poverty and low educational status, and air pollution. It is envisaged that herbal products that can stem this trend would be of great benefit. Garcinia kola (GK), also known as bitter kola is one of such plants. Generally used as a social snack and offered to guests in some cultural settings, bitter kola has been indicated in the treatment of laryngitis, general inflammation, bronchitis, viral infections and diabetes. In this study, the effects of methanol seed extract of Garcinia kola on the proliferation of Vascular Smooth Muscle Cells (VSMCs) in cell culture by Angiotensin II (Ang II) and LPS-induced NO production were carried out. Confluent VSMCs were exposed to GK (25, 50 and 100 μg/ml) before or after treatment with lipopolyssacharide (100μg/ml), and Angiotensin II (10-8-10-6M). Cellular proliferation was determined by MTT assay and NO production by Griess assay. Treatment with Angiotensin II (10-8, 10-6) or LPS significantly enhanced proliferation of VSM cells while LPS significantly increased nitric oxide (NO) production. Treatment with GK (25, 50 & 100 μg/ml) attenuated VSM cell proliferation. The results indicate that GK has potential to inhibit mitogen activated vascular cell growth and possibly inhibit inflammatory responses to LPS. Thus GK may be useful in condition that is characterized by cellular proliferation and inflammatory responses

Cardioprotective Effects of Curcumin-Nisin Based Poly Lactic Acid Nanoparticle on Myocardial Infarction in Guinea Pigs

Abstract Myocardial infarction (MI) is the most prevalent cause of cardiovascular death. A possible way of preventing MI maybe by dietary supplements. The present study was thus designed to ascertain the cardio-protective effect of a formulated curcumin and nisin based poly lactic acid nanoparticle (CurNisNp) on isoproterenol (ISO) induced MI in guinea pigs. Animals were pretreated for 7 days as follows; Groups A and B animals were given 0.5 mL/kg of normal saline, group C metoprolol (2 mg/kg), groups D and E CurNisNp 10 and 21 mg/kg respectively (n = 5). MI was induced on the 7th day in groups B-E animals. On the 9th day electrocardiogram (ECG) was recorded, blood samples and tissue biopsies were collected for analyses. Toxicity studies on CurNisNp were carried out. MI induction caused atrial fibrillation which was prevented by pretreatment of metoprolol or CurNisNp. MI induction was also associated with increased expressions of cardiac troponin I (CTnI) and kidney injury molecule-1 (KIM-1) which were significantly reduced in guinea pig’s pretreated with metoprolol or CurNisNp (P < 0.05). The LC50 of CurNisNp was 3258.2 μg/mL. This study demonstrated that the formulated curcumin-nisin based nanoparticle confers a significant level of cardio-protection in the guinea pig and is nontoxic

Methanol leaf extract of Momordica charantia protects alloxan-induced hepatopathy through modulation of caspase-9 and interleukin-1β signaling pathways in rats

Background and Aim: Momordica charantia is a highly valued plant, widely distributed in the tropical and subtropical regions. The plant is reported to have a wide range of medicinal uses. This study was designed to explore the ameliorative potential of M. charantia methanol leaf extract in alloxan-induced diabetic animal model with a particular focus on the liver. Materials and Methods: Hepatoprotective effect of methanol leaf extract of M. charantia was assessed in alloxan-induced toxicity in 50 rats divided into five groups (A-E) (n=10). Group A normal control, Group B was toxicant group, and Group C animals received glibenclamide treatment while Groups D and E received extracts at 200 and 400 mg/kg doses, respectively. The experiment lasted for 28 days. Histopathological changes, blood glucose level, and serum enzymes such as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, oxidative status and caspase-9, and interleukin-1β (IL-1β) were evaluated. Results: Extract-treatment caused a decreased blood glucose level, markers of oxidative stress such as malondialdehyde and hydrogen peroxide (H2O2). Treatment of rats with leaf extract of M. charantia resulted in increased levels and activities of protein thiols, non-protein thiols, glutathione (GSH), glutathione peroxidase, glutathione S-transferase, and superoxide dismutase indicating its antioxidant potential. The liver section revealed mild distortion of the hepatic architecture compared to the toxicant group, while decreased expressions of caspase-9 and IL-1β in extract-treated groups was observed. Conclusion: The plant extract exhibited antioxidant, anti-apoptotic, and anti-inflammatory effects, thus showing its hepatoprotective property

Methanol leaf extract of Momordica charantia protects alloxan-induced hepatopathy through modulation of caspase-9 and interleukin-1β signaling pathways in rats

Background and Aim: Momordica charantia is a highly valued plant, widely distributed in the tropical and subtropical regions. The plant is reported to have a wide range of medicinal uses. This study was designed to explore the ameliorative potential of M. charantia methanol leaf extract in alloxan-induced diabetic animal model with a particular focus on the liver. Materials and Methods: Hepatoprotective effect of methanol leaf extract of M. charantia was assessed in alloxan-induced toxicity in 50 rats divided into five groups (A-E) (n=10). Group A normal control, Group B was toxicant group, and Group C animals received glibenclamide treatment while Groups D and E received extracts at 200 and 400 mg/kg doses, respectively. The experiment lasted for 28 days. Histopathological changes, blood glucose level, and serum enzymes such as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, oxidative status and caspase-9, and interleukin-1β (IL-1β) were evaluated. Results: Extract-treatment caused a decreased blood glucose level, markers of oxidative stress such as malondialdehyde and hydrogen peroxide (H2O2). Treatment of rats with leaf extract of M. charantia resulted in increased levels and activities of protein thiols, non-protein thiols, glutathione (GSH), glutathione peroxidase, glutathione S-transferase, and superoxide dismutase indicating its antioxidant potential. The liver section revealed mild distortion of the hepatic architecture compared to the toxicant group, while decreased expressions of caspase-9 and IL-1β in extract-treated groups was observed. Conclusion: The plant extract exhibited antioxidant, anti-apoptotic, and anti-inflammatory effects, thus showing its hepatoprotective property