Targeting TNF-α and NF-κB Activation by Bee Venom: Role in
Suppressing Adjuvant Induced Arthritis and Methotrexate Hepatotoxicity in Rats
PLoS ONE, 11/20/2013
Low dose methotrexate is the cornerstone for the treatment
of rheumatoid arthritis. One of its major drawbacks is hepatotoxicity,
resulting in poor compliance of therapy. Dissatisfied arthritis patients are
likely to seek the option of complementary and alternative medicine such as bee
venom. The combination of natural products with modern medicine poses the
possibility of potential interaction between the two groups and needs
investigation.
The present study was aimed to investigate the modulatory
effect of bee venom acupuncture on efficacy, toxicity, and pharmacokinetics and
tissue disposition of methotrexate.
Complete Freund's adjuvant induced arthritic rats were
treated for 3 weeks with methotrexate and/or bee venom. Arthritic score, ankle
diameter, paw volume and tissue expression of NF-κB and TNF-α were determined
to assess anti-arthritic effects, while anti-nociceptive effects were assessed
by gait score and thermal hyperalgesia. Methotrexate toxicity was assessed by
measuring serum TNF-α, liver enzymes and expression of NF-κB in liver.
Combination therapy of bee venom with methotrexate
significantly improved arthritic parameters and analgesic effect as compared to
methotrexate alone. Bee venom ameliorated serum TNF-α and liver enzymes
elevations as well as over expression of NF-κB in liver induced by
methotrexate. Histological examination supported the results. And for the first
time bee venom acupuncture was approved to increase methotrexate bioavailability
with a significant decrease in its elimination.
Conclusion: bee venom potentiates the anti-arthritic effects
of methotrexate, possibly by increasing its bioavailability. Also, it provides
a potent anti-nociceptive effect. Furthermore, bee venom protects against
methotrexate induced hepatotoxicity mostly due to its inhibitory effect on
TNF-α and NF-κB.
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