Infliximab Ameliorates Methotrexate-Induced Nephrotoxicity in Experimental Rat Model: Impact on Oxidative Stress, Mitochondrial Biogenesis, Apoptotic and Autophagic Machineries.

Accumulating data confirms that Methotrexate (MTX), a well-known immunosuppressive and anticancer drug, causes nephrotoxicity. Infliximab (INF), the inhibitor of tumor necrosis factor-alpha (TNF-α), was proven to have anti-inflammatory properties. Thus, it may have potential in preventing MTX-induced nephrotoxicity. Therefore, this study aimed to inspect the prospective nephroprotective effect of INF on MTX-induced rat nephrotoxicity through investigating the possible molecular mechanisms, including its interference with different death routes, oxidative stress as well as mitochondrial biogenesis. Rats received an INF intraperitoneal single dose of 7 mg/kg 72 h prior to a single 20 mg/kg MTX injection. MTX nephrotoxicity was demonstrated by significantly increased serum levels of the renal indicators urea and creatinine as well as renal inflammatory markers TNF-α and Interleukin-6 (IL-6) and the renal oxidative stress marker malondialdehyde (MDA), while renal antioxidant enzyme superoxide dismutase (SOD) was significantly decreased compared to control. INF injection prior to MTX markedly reversed these MTX-induced effects. Besides, MTX impaired mitochondrial biogenesis, while INF attenuated this impairment, as indicated by increased expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). Finally, MTX triggered apoptotic and autophagic cascades in renal tissues as evidenced by reduced anti-apoptotic Bcl-2 protein expression as well as elevated expression of the pro-apoptotic protein Bax and both key regulators of autophagy; beclin-1 and LC-3, whereas INF pretreatment counteracted these apoptotic and autophagic effects of MTX. Summarily, these results suggest that INF provides protection against MTX-induced nephrotoxicity which could be elucidated by its antioxidant, anti-inflammatory, anti-apoptotic and anti-autophagic effects as well as upregulating mitochondrial biogenesis.

Bioactivity evaluation for volatiles and water extract of commercialized star anise.

BACKGROUND: Usually, it takes about a year since the harvested fresh star anise fruit (SAF) reaches the market for consumer usage, all this time with different handling processes and different storage circumstances greatly affect its quality as well as its chemical composition and biological activity. AIM: This study investigated the chemical constituents for volatiles and water extracts of commercialized SAF, as well as, their bioactivities. RESULTS: The chemical constituents were dominated by Trans-Anethole (47.16 %), estragole (14.4 %), and foeniculin (8.86 %) in the essential oils. Meanwhile, Coumarin, Apigenin, and Rosmarinic were the predominant phenolics of water extract. The result reflects a distinction of water extract to minimize mycotoxin secretion in liquid media. The SAF-volatiles were more effective in inhibiting microbial growth of the investigated bacterial and fungal strains. CONCLUSION: Although samples were commercially collected from markets, their extracts were still capable to inhibit up to 55 % of fungal growth. The SAF water extract exhibited a moderate and selective cytotoxic effect (IC50 = 114.9 µg/ml) against HepG2 cell lines compared to the low impact of essential oil (IC50 = 513.8 µg/ml). Which led to the conclusion that despite the long-time span for SAF till it reaches the market, aqueous extract maintained a good ability for reducing mycotoxins-secretion from fungi grown in liquid media. This result emphasizes the role of the phenolics of water extracts' as an anti-mycotoxigenic agent.

Malignant tumors could be misinterpreted as temporomandibular joint disorders.

OBJECTIVES: This article stresses the importance of exclusion of malignant tumors as a cause of temporomandibular joint disorder, which is usually caused by intra-articular or musculoligamental dysfunction without considering malignant tumors as a cause of such complaints. METHOD AND RESULTS: Three patients were referred to us because of persistent and recurrent temporomandibular joint dysfunction. All patients were treated more than once through their general practitioner, ear nose and throat physician, or dental physician without significant improvement. After adequate clinical and radiological examination, malignant tumors were discovered as a cause of such complaints. CONCLUSIONS: Patients with primary or secondary tumors could present with symptoms simulating temporomandibular joint disorder and will therefore be treated similarly. In such condition, missing that rare cause will consequently lead to unnecessary delayed diagnosis and may cost the patients their lives.