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An adjuvant effect of Metformin as an anti-fibrotic agent when administered with the anti-schistosomal Praziquantel in Schistosoma mansoni infected mice

Salama WM, El-Naggar SA, Harras SF, El-Said KS

Trop Biomed, 2021 Jun 01;38(2):205-213.
PMID: 34172712 DOI: 10.47665/tb.38.2.059

Schistosomiasis is the second most common parasitic disease post Malaria around the world. Praziquantel (PZQ) is known as the most efficient anti- schistosomal drug but has no anti-fibrotic effect. Metformin (Met) is a well-known drug for type 2 diabetes. This study aimed to evaluate the role of Met as anti-schistosomal and anti-fibrotic agents alone or in combination with PZQ treatment. Forty male CD1 mice were divided into four groups (n=10 mice) as following; the first group (Gp1) was served as a negative control. Gp2, Gp3, Gp4, and Gp5 were infected with (60-80) S. mansoni cercariae. After a month of infection, Gp3 was administered orally with PZQ (500 mg/Kg) for 2 consecutive days. Gp4 was administered orally with Met (150 mg/Kg) for 15 consecutive days, and Gp5 was orally administered with PZQ followed by Met for 15 consecutive days at the same doses as in Gp 3 and 4. The results showed that PZQ had potent worms and egg reduction in liver and intestine tissues with no anti-fibrotic effect of the granuloma formation. However, Met or PZQ/Met treatment postinfection led to a reduction in egg count in both liver and intestine tissues with a significant reduction in granuloma site. Treatment of S. mansoni-infected mice with Met or PZQ/Met ameliorated the hematological and biochemical alterations induced by S. mansoni infection. Collectively, Met has no anti-schistosomal activity but led to a reduction in egg deposition and showed an anti-fibrotic effect on granulomatous development either when used alone or in combination with PZQ treatment. This study shed light on the possible role of Met as an anti-fibrotic agent when administered with PZQ for S. mansoni infected humans.

Matched MeSH terms: Adjuvants, Pharmaceutic/therapeutic use
Treatment of preeclampsia with hydroxychloroquine: a review

Abd Rahman R, DeKoninck P, Murthi P, Wallace EM

J Matern Fetal Neonatal Med, 2018 Feb;31(4):525-529.
PMID: 28142291 DOI: 10.1080/14767058.2017.1289511

In this review, we discuss the potential use of antimalarial drugs as an adjuvant therapy for preeclampsia, focusing on the mechanisms of action of this class of drugs in the context of preeclampsia. In particular, hydroxychloroquine has been shown to have various beneficial effects on patients with systemic lupus erythematosus. There are several pathways targeted by the antimalarial drugs that are similar to the pathophysiology of preeclampsia and hence offering opportunities to develop novel therapies to treat the disease. Given the safety profile of hydroxychloroquine in pregnancy, there is merit in exploring the efficacy of this drug as an adjuvant therapy in women with early onset preeclampsia.

Matched MeSH terms: Adjuvants, Pharmaceutic/therapeutic use
Fulltext The intraperitoneal ondansetron for postoperative pain management following laparoscopic cholecystectomy: A proof-of-concept, double-blind, placebo-controlled trial

Abdelaziz DH, Boraii S, Cheema E, Elnaem MH, Omar T, Abdelraouf A, et al.

Biomed Pharmacother, 2021 Aug;140:111725.
PMID: 34015580 DOI: 10.1016/j.biopha.2021.111725

BACKGROUND: Pain after laparoscopic cholecystectomy remains a major challenge. Ondansetron blocks sodium channels and may have local anesthetic properties.
AIMS: To investigate the effect of intraperitoneal administration of ondansetron for postoperative pain management as an adjuvant to intravenous acetaminophen in patients undergoing laparoscopic cholecystectomy.
METHODS: Patients scheduled for elective laparoscopic cholecystectomy were randomized into two groups (n = 25 each) to receive either intraperitoneal ondansetron or saline injected in the gall bladder bed at the end of the procedure. The primary outcome was the difference in pain from baseline to 24-h post-operative assessed by comparing the area under the curve of visual analog score between the two groups.
RESULTS: The derived area under response curve of visual analog scores in the ondansetron group (735.8 ± 418.3) was 33.97% lower than (p = 0.005) that calculated for the control group (1114.4 ± 423.9). The need for rescue analgesia was significantly lower in the ondansetron (16%) versus in the control group (54.17%) (p = 0.005), indicating better pain control. The correlation between the time for unassisted mobilization and the area under response curve of visual analog scores signified the positive analgesic influence of ondansetron (rs =0.315, p = 0.028). The frequency of nausea and vomiting was significantly lower in patients who received ondansetron than that reported in the control group (p = 0.023 (8 h), and 0.016 (24 h) respectively).
CONCLUSIONS: The added positive impact of ondansetron on postoperative pain control alongside its anti-emetic effect made it a unique novel option for patients undergoing laparoscopic cholecystectomy.

Matched MeSH terms: Adjuvants, Pharmaceutic/therapeutic use*
Copper supplementation amplifies the anti-tumor effect of curcumin in oral cancer cells

Lee HM, Patel V, Shyur LF, Lee WL

Phytomedicine, 2016 Nov 15;23(12):1535-1544.
PMID: 27765374 DOI: 10.1016/j.phymed.2016.09.005

BACKGROUND: Oral cancer is the sixth most common cancer worldwide and 90% of oral malignancies are caused by oral squamous cell carcinoma (OSCC). Curcumin, a phytocompound derived from turmeric (Curcuma longa) was observed to have anti-cancer activity which can be developed as an alternative treatment option for OSCC. However, OSCC cells with various clinical-pathological features respond differentially to curcumin treatment.
HYPOTHESIS: Intracellular copper levels have been reported to correlate with tumor pathogenesis and affect the sensitivity of cancer cells to cytotoxic chemotherapy. We hypothesized that intracellular copper levels may affect the sensitivity of oral cancer cells to curcumin.
METHODS: We analysed the correlation between intracellular copper levels and response to curcumin treatment in a panel of OSCC cell lines derived from oral cancer patients. Exogenous copper was supplemented in curcumin insensitive cell lines to observe the effect of copper on curcumin-mediated inhibition of cell viability and migration, as well as induction of oxidative stress and apoptosis. Protein markers of cell migration and oxidative stress were also analysed using Western blotting.
RESULTS: Concentrations of curcumin which inhibited 50% OSCC cell viability (IC50) was reduced up to 5 times in the presence of 250 µM copper. Increased copper level in curcumin-treated OSCC cells was accompanied by the induction of intracellular ROS and increased level of Nrf2 which regulates oxidative stress responses in cells. Supplemental copper also inhibited migration of curcumin-treated cells with enhanced level of E-cadherin and decreased vimentin, indications of suppressed epithelial-mesenchymal transition. Early apoptosis was observed in combined treatment but not in treatment with curcumin or copper alone.
CONCLUSION: Supplement of copper significantly enhanced the inhibitory effect of curcumin treatment on migration and viability of oral cancer cells. Together, these findings provide molecular insight into the role of copper in overcoming insensitivity of oral cancer cells to curcumin treatment, suggesting a new strategy for cancer therapy.

Matched MeSH terms: Adjuvants, Pharmaceutic/therapeutic use*