Pharmacolgy

To evaluate the effectiveness of Nigella sativa (NS) in the prevention of hepatotoxicity of large doses of methotrexate (MTX) (IP) in rabbits. Methods: Three groups of male rabbits, six in each were used. Oral dosing was administered as a paste; formula 1 was prepared by mixing 2 g fl our with water; formula 2 contained fl our and NS and water. Group 1 was fed with formula 1 daily and injected with 2 ml/kg normal saline IP. Group 2 was given formula 1 daily with 20 mg/kg MTX IP. Group 3 was fed with formula 2 daily + MTX 20 mg/kg IP. Injections were given weekly for 5 weeks, and then the animals were sacrifi ced at day 39. Liver enzymes, malondialdehyde (MDA), glutathione (GSH), and histopathology of the liver were evaluated. Results: Liver enzymes, serum, and liver MDA were signifi cantly increased by MTX. MTX + NS treatment signifi cantly reduced the rise in liver enzymes, MDA in serum with little effect on liver MDA. Serum aspartate aminotransferase, alkaline phosphatase, and bilirubin were reduced from 82.8±18.04 U/L, 4.9±2.0 kind and king unit/100 ml and 0.74±0.1 mg/dl to 56.1±7.5, 2.0±0.6 and 0.27±0.1 respectively. Unexpectedly, serum and liver GSH were slightly increased by MTX. Treatment with MTX + NS further increased these levels. Histologically, portal and lobular sinusoidal dilatation, lymphocytic infi ltration, and hepatocyte hydropic degeneration were seen in all rabbits on MTX, which disappeared in three rabbits on NS + MTX. Conclusion: NS is hepatoprotective against MTX induced hepatotoxicity.

Background: Overdose of paracetamol (PCM) is reported to cause hepatotoxicity and nephrotoxicity, or nephrotoxicity in absence of hepatotoxicity. This study was planned to investigate hepatotoxicity or nephrotoxicity induced by PCM. Methods: Two groups of rabbits, six rabbits in each were used; control group were treated with normal saline, the second group was treated with PCM 1 g/kg/day orally for 9 days. Results: PCM lead to a significant rise in serum liver enzymes, aspartate aminotransferase, alanine transaminase, alkaline phosphatase and total bilirubin with an increase in serum level of malondialdehyde (MDA) and reduction in serum glutathione (GSH). MDA level in liver homogenate was also significantly increased. These findings were further confirmed by histopathological changes suggestive of severe liver damage. On the contrary, PCM slightly increased serum creatinine, without changing MDA and GSH in kidney homogenate. Lack of PCM nephrotoxicity was further confirmed by histopathological examination. Conclusion: PCM overdose produced severe hepatotoxicity without affecting the kidneys of the rabbits

Background: Animal models are important tools for studying drug-induced toxicity. Species differences in drug-induced nephrotoxicity or hepatotoxicity was frequently reported, however, clear evidence of species differences in nephrotoxicity or hepatotoxicity induced by methotrexate (MTX) is not available. Aim: The present study was designed to investigate nephrotoxicity or hepatotoxicity of MTX in mice and rabbits. Methodology: twelve rabbits and 16 mice were used for the study. Each species of animals was divided into 2 groups; control and MTX treated groups. The control groups were treated with normal saline intra-peritoneum (IP), MTX was given IP in a dose of 20 mg/kg/weekly for 38 days for the rabbits and at a dose of 10mg/kg/ weekly for 23 days for mice. Serum levels of liver enzymes, urea, creatinine, Malondialdehyde (MDA) and MDA in liver homogenate were estimated for the rabbits. In mice, glutathione (GSH) and MDA were estimated in liver and kidney homogenates. Histopathological examination of the kidney and liver was done for the 2 species. Results: In the rabbits, MTX resulted in a significant increase in liver enzymes, and in MDA levels of serum, liver and kidney homogenates, while the levels of urea and creatinine were not affected. Histopathological changes suggestive of liver damage were seen, while the kidneys appeared normal on histopathological examination. In the mice, MTX resulted in a significant increase in MDA in the liver homogenates with a small and insignificant reduction in GSH. In mice kidney homogenates, MTX had not affected MDA, while GSH was significantly reduced. Histopathological examination in mice showed significant damage in both liver and kidney. Conclusion: MTX produced hepatotoxicity in rabbits and mice but nephrotoxicity occurred in mice only. This suggests that rabbits might be resistant to MTX induced nephrotoxicity.

Background: Animal models are important tools for studying drug-induced toxicity. Species differences in drug-induced nephrotoxicity or hepatotoxicity was frequently reported, however, clear evidence of species differences in nephrotoxicity or hepatotoxicity induced by methotrexate (MTX) is not available. Aim: The present study was designed to investigate nephrotoxicity or hepatotoxicity of MTX in mice and rabbits. Methodology: twelve rabbits and 16 mice were used for the study. Each species of animals was divided into 2 groups; control and MTX treated groups. The control groups were treated with normal saline intraperitoneum (IP), MTX was given IP in a dose of 20 mg/kg/weekly for 38 days for the rabbits and at a dose of 10mg/kg/ weekly for 23 days for mice. Serum levels of liver enzymes, urea, creatinine, Malondialdehyde (MDA) and MDA in liver homogenate were estimated for the rabbits. In mice, glutathione (GSH) and MDA were estimated in liver and kidney homogenates. Histopathological examination of the kidney and liver was done for the 2 species. Results: In the rabbits, MTX resulted in a significant increase in liver enzymes, and in MDA levels of serum, liver and kidney homogenates, while the levels of urea and creatinine were not affected. Histopathological changes suggestive of liver damage were seen, while the kidneys appeared normal on histopathological examination. In the mice, MTX resulted in a significant increase in MDA in the liver homogenates with a small and insignificant reduction in GSH. In mice kidney homogenates, MTX had not affected MDA, while GSH was significantly reduced. Histopathological examination in mice showed significant damage in both liver and kidney. Conclusion: MTX produced hepatotoxicity in rabbits and mice but nephrotoxicity occurred in mice only. This suggests that rabbits might be resistant to MTX induced nephrotoxicity.

Background: Overdose of paracetamol (PCM) is reported to cause hepatotoxicity and nephrotoxicity, or nephrotoxicity in absence of hepatotoxicity. This study was planned to investigate hepatotoxicity or nephrotoxicity induced by PCM. Methods: Two groups of rabbits, six rabbits in each were used; control group were treated with normal saline, the second group was treated with PCM 1 g/kg/day orally for 9 days. Results: PCM lead to a significant rise in serum liver enzymes, aspartate aminotransferase, alanine transaminase, alkaline phosphatase and total bilirubin with an increase in serum level of malondialdehyde (MDA) and reduction in serum glutathione (GSH). MDA level in liver homogenate was also significantly increased. These findings were further confirmed by histopathological changes suggestive of severe liver damage. On the contrary, PCM slightly increased serum creatinine, without changing MDA and GSH in kidney homogenate. Lack of PCM nephrotoxicity was further confirmed by histopathological examination. Conclusion: PCM overdose produced severe hepatotoxicity without affecting the kidneys of the rabbits

Hepatotoxicity is a real challenge to physicians concerned intuberculosis treatment. It is frequently blamed for therapy failure and emergence of bacterial resistance and sometimes fatal. In the absence of a drug which can prevent hepatotoxicity, herbal medications offer an alternative remedy to minimize this side effect. The study was designed to evaluate the effect ofNigella sativa (NS), a medicinal plant known for its hepatoprotective effect against hepatotoxicity induced by Pyrazinamide (PZA) 350 mg/kg alone or in combination with other anti-tuberculosis drugs (anti-TB). Anti-TB drugs contain PZA 350 mg/kg + INH 50 mg/kg + Rifampicin (RIF) 100 mg/kg.Six groups of rabbits (6 animals in each) were treated orally for 12 days as follow: Normal saline (control), NS, PZA, (PZA+NS), (Anti-TB drugs), and (Anti-TB + NS). Liver enzymes, S. Glutathione (GSH), liver tissue (GSH) and Malondialdehyde (MDA) were estimated and liver histology was examined. PZA and anti-TB drugs increased liver enzymes, increased MDA and decreased GSH with histopathological changes suggestive of hepatotoxicity. Treatment with NS significantly changed liver enzymes, GSH, MDA and histopathological changes toward normal values. Conclusions: NS due to its antioxidant effect is protective against hepatotoxicity induced by PZA and anti-TB drugs.

Recently, significant progress has been made through the application of peroxisome pro-liferator activated receptor-c (PPAR-c) agonists as anti-inflammatory drugs that are efficacious, relatively free of side effects, and can be used effectively for a long time. The present study was designed to evaluate the dose–response relationship of the anti-inflammatory activity of telmisartan in rat models of chronic inflammation. The study protocol includes four stages: First stage: 48 rats were allocated into eight groups, each containing six rats, for the study of the anti-inflammatory activity of different doses of telmisartan in rat model of formaldehyde-induced chronic inflammation. Second stage: six rats were used to study the anti-inflammatory activity of telmisartan (1.5 mg/ kg) in combination with dexamethasone (0.5 mg/kg) in the same model. Third stage: 48 rats were allocated into eight groups, each containing six rats, for the study of the anti-inflammatory activity of telmisartan in rat model of cotton pellet-induced granuloma. Fourth stage: six rats were used to study the anti-inflammatory activity of telmisartan (1.5 mg/kg) when used as adjuvant with dexa-methasone (0.5 mg/kg) in the same model. Telmisartan in a dose-dependent pattern (0.1, 0.2. 0.4, 0.6, 1.5, 3 mg/kg) significantly suppressed inflammation in rat models of formaldehyde-induced chronic inflammation and cotton pellet-induced granuloma. When combined with dexamethasone, telmisartan (1.5 mg/kg body weight) significantly suppressed inflammation in both models, which is significantly higher than all of the effects produced by other approaches of treatment when telmi-sartan used alone. In conclusion, telmisartan decreased formaldehyde-induced chronic inflammation and cotton-pellet induced granuloma in rats in a dose-dependent pattern. Therefore, it may be considered as a potential treatment for chronic inflammatory conditions in human.