Abstract
Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) mostly associated with renal and hepatic adverse effects, and the adjunct use of compounds with potent protective effects, like silymarin, may be one of the choices to avoid these effects. This project was designed to evaluate the protective effect of silymarin against the suspected renal and hepatic injury induced with long term use of NSAIDs; 220 patients with osteoarthritis were randomized into 5 groups and treated with either silymarin 300mg/day alone, piroxicam 20mg/day alone, meloxicam 15mg/day alone or the combination of each of them with silymarin for 8 weeks. The renal and hepatic functions were evaluated before starting treatment and after 8 weeks including assessment of serum levels of urea, creatinine and the activities of the hepatic enzymes alkaline phosphatase (ALP), glutamic-oxalic acid transaminase (GOT) and glutamic-pyruvic acid transaminase (GPT). The results indicated that using NSAIDs alone produced elevation in the markers of renal and hepatic damage that can be successfully prevented or reversed when silymarin adjunctly used with them. In conclusion, silymarin when co-administered with the NSAIDs (piroxicam or meloxicam) decreases their renal and hepatic toxicities in OA patients.
 Key words: Silymarin; Piroxicam, Meloxicam; Nephroprotection; Hepatoprotection
Highlights
Many physiological functions other than inflammation are reported for prostaglandins (PGs) including maintenance of gastromucosal integrity,(1) modulation of renal microvascular hemodynamics and tubular salts and water reabsorption.[2]
The results presented in table 1 indicated that serum levels of urea and creatinine are within normal values, treatment with (300mg/day) silymarin for 8 weeks resulted in significant reduction in the serum levels of both parameters
Combination of both non-steroidal antiinflammatory drugs (NSAIDs) used with 300mg/day of silymarin resulted in significant reduction in the activities of liver enzymes in the serum after 8 weeks, where alkaline phosphatase (ALP) activity significantly reduced by 20% and 24% respectively, glutamic-oxalic acid transaminase (GOT) activity was reduced by 28.5% and 50% respectively, and glutamic-pyruvic acid transaminase (GPT) activity was reduced by 33% and 35% respectively compared to the pre-treatment values .Analysis of inter group variations using ANOVA revealed significant difference among groups in this respect (P
Summary
Many physiological functions other than inflammation are reported for prostaglandins (PGs) including maintenance of gastromucosal integrity,(1) modulation of renal microvascular hemodynamics and tubular salts and water reabsorption.[2] So, nephrotoxicity, gastropathy and other forms of tissue injury are reported as a result of long-term use of non-steroidal antiinflammatory drugs (NSAIDs) ( both selective and non-selective cyclooxygenase inhibitors),(3). Considered as an important parameter during long-term therapy.[4] According to the available reports, all NSAIDs, selective and non-selective COX inhibitors, share relatively the same therapeutic and adverse effects profile, and caution should be exercised with their use; adjuvant cytoprotection should be considered.[5, 6] Silymarin is a mixture of flavolignans isolated from the ripe seeds of the medicinal plant Silybum marianum (Milk thistle).(7) It has many pharmacological activities including anticancer,(8).
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