Evaluation of safety and efficacy profile of Nigella sativa oil as an add-on therapy, in addition to alpha-keto analogue of essential amino acids in patients with chronic kidney disease.

Chronic kidney disease (CKD) encompasses a spectrum of different pathophysio- logic processes associated with abnormal kidney function. When it reaches end-stage renal disease (ESRD), the only option is dialysis and renal transplantation. This is unaffordable by most patients. Hence, newer treatment modalities are being looked for, which can slow down the progression of CKD and delay the development of ESRD. This study aimed to evaluate the efficacy and safety of Nigella sativa oil as an add-on therapy in addition to alpha-keto analogue of essential amino acids in patients with CKD Stages 3 and 4. The study was conducted at a tertiary care center in North India on patients with CKD Stages 3 and 4. It was a prospective, comparative, and open-labeled study. One hundred and fifty patients were enrolled and were randomly divided into two interventional groups. Fourteen patients were lost to follow-up. Group I (control) which had 66 patients received conservative management of CKD consisting of alpha-keto analogue (600 mg tablet three times a day), whereas Group II (test) which had 70 patients received conservative management along with alpha-keto analogue and N. sativa oil (2.5 mL, per orally, once daily) for 12 weeks. Hemogram, renal function, and serum electrolyte tests were done, and adverse events were recorded at baseline and at4, 8, and 12 weeks of treatment. After 12 weeks of treatment, there was a marked improvement in clinical features and biochemical parameters in both the control and test groups. There were a significant reduction in blood urea, serum creatinine, and 24-h total urine protein and a significant improvement in 24-h total urine volume and glomerular filtration rate. N. sativa oil supplementation along with alpha-keto analogue is more more efficacious and safe in delaying the progression of disease patients with CKD Stages 3 and 4.

Pharmacoenvironmentology--a component of pharmacovigilance.

According to WHO, Pharmacovigilance activities are done to monitor detection, assessment, understanding and prevention of any obnoxious adverse reactions to drugs at therapeutic concentration on animal and human beings. However, there is also a growing focus among scientists and environmentalists about the impact of drugs on environment and surroundings. The existing term 'Ecopharmacology' is too broad and not even defined in a clear manner. The term 'Pharmacoenvironmentology' seeks to deal with the environmental impact of drugs given to humans and animals at therapeutic doses.

Protective role of Nigella sativa in diabetic nephropathy: A randomized clinical trial.

This study aims to evaluate efficacy and safety of Nigella sativa oil supplementation in patients with chronic kidney disease Stage 3 and 4 due to diabetic nephropathy. It was a prospective, comparative, and open-label study. Patients were randomized into two groups. Group 1 (Control) received conservative management of diabetic nephropathy, whereas Group 2 (Test) received N. sativa oil (2.5 mL, once daily and per orally) along with conservative management for 12 weeks. Blood glucose, hemogram, and kidney function test were done at 0, 6, and 12 weeks of treatment. Significance of differences between pre- and post-treatment values in each group was assessed using Student's paired t-test and between the groups using unpaired t-test. We found a drop in blood glucose, serum creatinine, blood urea, and 24 h total urinary protein levels and a rise in glomerular filtration rate, 24 h total urinary volume, and hemoglobin level in the treatment group compared to the control group.

Amelioration of cisplatin-induced nephrotoxicity by ethanolic extract of Bauhinia purpurea: An in vivo study in rats.

Our objective is to study the nephroprotective activity and antioxidant potential of Bauhinia purpurea unripe pods and bark against cisplatin-induced nephrotoxicity. Healthy adult albino rats of either sex (150-200 g) were randomly divided into six groups of six animals each Group I (vehicle control) and Group II (negative control). Group III (BBE200) and Group IV (BBE400) were administered the ethanolic extract of Bauhinia purpurea bark in doses of 200 and 400 mg/kg/day p.o., respectively, and Group V (BPE200) and Group VI (BPE400) were administered the ethanolic extract of Bauhinia purpurea unripe pods at doses of 200 and 400 mg/kg/day p.o., respectively. All the treatments were given for nine days. Cisplatin in a single dose of 6 mg/kg i.p. was given on the 4 th day to all groups, except the vehicle control group. On the 10 th day, blood and urine were collected for biochemical tests and the rats were sacrificed. The kidney was removed for histology and lipid peroxidation-antioxidant test. Cisplatin caused nephrotoxicity as evidenced by elevated blood urea, serum creatinine and urine glucose, and there was decreased creatinine clearance in Group II as compared with Group I. Administration of BBE and BPE at doses of 200 and 400 mg/kg in Group III and Group VI caused a dose-dependant reduction in the rise of blood urea, serum creatinine and urine glucose, and there was a dose-dependant increase in creatinine clearance compared with Group II. There was increased catalase and glutathione and decreased malondialdehyde levels in Group II, while BBE 400 (Group IV) and BPE 400 (Group VI) treatments significantly reversed the changes toward normal values. Histological examination of the kidney revealed protection in Group IV and Group VI compared with Group II. The ethanolic extract of Bauhinia purpurea unripe pods and bark has a nephroprotective activity against cisplatin-induced nephrotoxicity in rats.

Statin induced diabetes and its clinical implications.

Statins are one of the most commonly used drugs in the world based on their potential to prevent adverse cardiovascular events. These cholesterol-lowering drugs received a US Food and Drug Administration warning, in February 2012, regarding increased risk of incident diabetes and impaired glycemic control in patients who already have diabetes. The possible association of diabetes with statin therapy has started a wave of discussion in the medical community. A number of meta-analyses conducted in recent years have demonstrated that the association is real although causality has not been proved yet. Individual statins differ with respect to their diabetogenic property; women and elderly persons appear to be at increased risk. Various aspects of statin's adverse effect on glycemic control remain to be explored. As further research in this area continues, physicians might still take some precautions to make risk benefit ratio more favorable for the patients.

Biochemical and histopathological evaluation of histamine receptors (H1R, H2R, H3R and H4R)-agonist in rabbits.

The present study was designed to investigate the biochemical and histopathological changes in the livers of rabbits treated with histamine and histamine receptors (H1R-H4R)-agonist. The cohort comprised of six groups containing five rabbits each. Control group received sterile distilled water (1 mL/kg × b.i.d.) and treated groups received subcutaneous histamine (100 µg/kg × b.i.d.) and H1R-H4R-agonist (histamine trifluoro-methyl toluidide, amthamine, R-[-]-α-methylhistamine, clobenpropit, respectively) each in a dose of 10 µg/kg × b.i.d. (12 h [8 am and 8 pm]) for 30 days. Hepatotoxicity due to these agonists was analyzed using biochemical and histopathological methods. Histamine and H1R-H3R-agonist were found to be hepatotoxic as shown by statistically significant (p < 0.05) elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), most marked in the H3R-agonist group. However, their levels in H4R-agonist group remained very similar to the control group. The entire drug treated groups as compared to control showed significant elevated levels of alkaline phosphatase (ALP). Histopathological examination revealed obvious changes in histamine, H2R- and H3R-agonist groups in terms of alteration of hepatic microstructure, congestion, focal necrosis and increased incidence of multinucleate hepatocytes while H1R and H4R groups showed minimal changes. From the findings of the present study it may be concluded that on repeated administration, histamine and HR-agonists-induced hepatotoxicity which is most pronounced with H3R-agonist though not severe enough to jeopardize the vital functions of liver and warrants further long-term studies.

Dose-dependent effect of histamine on liver function markers in immunized rabbits.

OBJECTIVE: The present study was designed to delineate the hepatotoxicological roles of histamine dose-dependently in immunized rabbits. METHODS: The cohort comprised of three groups (II, III and IV), containing 18 rabbits each, and received subcutaneous histamine 50 µg/kg, 100 µg/kg and 200 µg/kg, respectively for 10 days (b.i.d., starting from 3 days prior to immunization until 7 days after immunization). Group I (control, n=18) received subcutaneous sterile distilled water for 10 days. They were subsequently immunized at day 3 with intravenous injection of SRBC (1×10(9) cells/ml). Blood samples were collected on pre-immunization (pre-I) day 0, as well as on days 7-, 14-, 21-, 28- and 58-post-immunization (post-I). Biochemical parameters aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin [total bilirubin (TB), direct bilirubin (DB) and indirect bilirubin (IB)] were determined. RESULTS: Groups II and IV revealed a significant decrease (on day 0-pre-I) and a significant increase (on days 7-, 14-, 21-, 28- and 58-post-I) in ALT and AST levels, when compared with the corresponding values of groups I and III while group II showed a significant increase in ALT and AST levels as compared to group IV. ALP levels in groups II, III and IV showed a significant enhancement when compared with group I. Moreover, results of TB, DB and IB demonstrated increased levels in group III when compared with groups I, II and IV. The results were found statistically significant (p<0.05). CONCLUSION: Short-term treatment of histamine produces dose-dependent differential patterns of hepatic dysfunctions suggestive mild liver degeneration warranting further long-term studies.

Immunological, biochemical and histopathological evaluation of histamine receptors (H1R, H2R, H3R and H4R)-antagonist in rabbit experimental model: a short term study.

The present study was designed to delineate the immuno- and hepatotoxicological roles of HRs-antagonists in vivo which is elementary in existing literature. The cohort comprised of two experimental studies. Experimental study 1 was designed for immunological investigations and consisted of seven groups and immunized with intravenous injection of SRBC at day 3 containing six rabbits each. Experimental study 2 was designed to assess the functional status of liver and comprised of seven groups containing five rabbits each. In both experimental studies group-I received sterile distilled water intramuscularly, and group II-VI received subcutaneous histamine, pheniramine (H1R-antagonist), ranitidine (H2R-antagonist), iodophenpropit (H3R-antagonist) and JNJ7777120 (H4R-antagonist), respectively while group-VII received DMSO intramuscularly. ELISA was used to assess the immunological investigations. The SRBC-specific immunoglobulins (Igs), IgM and IgG were significantly increased (p<0.05). Hepatotoxicity due to same histamine and HRs-antagonists were demonstrated by biochemical and histopathological methods. Rabbits in group II-VI had significantly (p<0.05) elevated levels of serum enzymes (ALT, AST, ALP) and bilirubin. Histopathological examination showed maintained hepatic lobular architecture in histamine and DMSO-treated groups a kin to control. Notable findings in other groups included increased binuclearity in H1R, trinuclearity in H2R, oxyphilic clusters of hepatocytes in H3R and moderate centrilobular necrosis in H3R and H4R-antagonist-treated groups without obvious inflammatory cell infiltration and Kupffer cell prominence. It is concluded that HRs-antagonist play immune suppressive role through H1R, H2R and H4R while immune enhancing role through H3R. In addition, HRs-antagonists appear moderately hepatotoxic in terms of altered serum enzyme levels and non-inflammatory hepatocellular damage.

The Influence of histamine H1-receptor on liver functions in immunized rabbits.

This study was designed to investigate the functional roles of histamine and histamine H1-receptor agonist and antagonist in the development of liver function impairment in immunized rabbits. The study comprised of six groups containing 18 rabbits each. Group III-VI received histamine (100 µg/kg, s.c.), H1R-agonist (HTMT, 10 µg/kg, s.c.), H1R-antagonist (pheniramine, 10 mg/kg, i.m.), and H1R-antagonist (pheniramine, 10 mg/kg, i.m.) plus histamine (100 µg/kg, s.c.), respectively, b.i.d. for 10 days. Group I (negative control) and group II (positive control) received sterile distilled water intramuscularly b.i.d. for 10 days. Groups II-VI were immunized on day 3 with intravenous injection of SRBC (1 × 10(9) cells/ml). Blood samples were collected on pre-immunization day 0, as well as on days 7-, 14-, 21-, 28-, and 58-post-immunization. Biochemical parameters AST, ALT, alkaline phosphatase and bilirubin [total bilirubin (TB), direct bilirubin (DB), and indirect bilirubin (IB)] were determined. On each experimental day, the mean values of serum enzymes and bilirubin in group I and group II showed no significant changes while in group III, IV, V, and VI, these enzymes and bilirubin levels showed significant changes (p < 0.05), when compared with their experimental values within the group. The levels of serum enzymes and bilirubin showed significant difference (p < 0.05) in group III, IV, V, and VI on each experimental day, when compared with the corresponding values of each other, and also compared with the corresponding values of group I and II. Histamine, HTMT, pheniramine, and combination of histamine + pheniramine cause hepatic function impairment in terms of altered serum enzymes and bilirubin levels. The present findings suggest that HTMT causes moderate liver function impairment while others show mild impairment.

Effect of Nigella sativa oil on various clinical and biochemical parameters of insulin resistance syndrome.

AIM: The seeds of the Nigella sativa plant have been used to promote health and fight disease for centuries, especially in the Middle East and in Southeast Asia. This plant has been a focus of much research. This clinical study was undertaken to know the adjuvant effect of N. sativa oil on various clinical and biochemical parameters of the insulin resistance syndrome. MATERIALS AND METHODS: This prospective study was conducted at a tertiary health care center in North India. After confirmation of diagnosis, 60 patients who fulfilled the inclusion and exclusion criteria were enrolled in this study. Written informed consent was taken from all the patients enrolled. Approval from the institutional ethical committee was also obtained. The patients were divided into two groups of 30 each. In group I (the standard group), patients were advised tablet atorvastatin 10 mg once a day and tablet metformin 500 mg twice a day for a period of 6 weeks. In group II (the N. sativa group), the patients were advised tablet atorvastatin 10 mg once a day, tablet metformin 500 mg twice a day, and N. sativa oil 2.5 ml twice daily for a period of 6 weeks. Fasting and postprandial blood glucose, fasting lipid profile, and waist circumference were recorded before therapy and after completion of therapy. RESULT: The treatment group showed significant (P < 0.05) improvement with reference to total cholesterol, low density lipoprotein cholesterol (LDL-C), and fasting blood glucose (P < 0.05). CONCLUSION: N. sativa oil was found to be effective as an add-on therapy in patients of insulin resistance syndrome. N. sativa oil has a significant activity in diabetic and dyslipidemic patients.