Background: Melittin is one of the most studied antimicrobial peptides, and severalin vitroexperiments have demonstrated its antibacterial efficacy. However, there is evidence showing melittin has non-promising effects such as cytotoxicity and hemolysis. Therefore, concerns about unwanted collateral toxicity of melittin lie ahead in the path toward its clinical development. With these considerations, the present study aimed to fill the gap betweenin vitroandin vivostudies.Methods: In the first step,in vitrotoxicity profile of melittin was assessed using cytotoxicity and hemolysis tests. Next, a maximum intraperitoneal (i.p.) sub-lethal dose was determined using BALB/c mice. Besides toxicity, antimicrobial efficacy of melittin against extensively drug-resistant (XDR)Acinetobacter baumannii, methicillin-resistantStaphylococcus aureus(MRSA), and KPC-producingKlebsiella pneumonia(KPC-KP) pathogens were tested using bothin vitroandin vivomethods.Results: Melittin showed extensive hemolysis (HD₅₀ = 0.44 µg/mL), and cytotoxicity (IC₅₀ = 6.45 µg/mL) activities with i.p. LD₅₀value of 4.98 mg/kg in BALB/c mice.In vitroantimicrobial evaluation showed melittin MIC range from 8 to 32 µg/mL for the studied pathogens. Treatment of infected mice with repeated sub-lethal doses of melittin (2.4 mg/kg) displayed no beneficial effect on their survival and peritoneal bacterial loads.Conclusions: These results indicate that melittin at its safe dose could not exhibit antimicrobial activity, which hinders its application in clinical practice.

Background: Side effects of cisplatin (CIS) such as testicular toxicity restrict its clinical use. Instead, evidence indicates that crocin (CR) has synergistic anti-cancer potential with CIS and exhibited beneficial effects on CIS-induced hepatorenal damage. The aim of this study was to investigate the protective potential of CR against CIS-induced testicular toxicity in rats.Methods: Fifty adult male Wistar rats randomly assigned to five equal groups including control, CIS, and CIS plus CR at doses of 6.25 mg/kg (CIS + CR6.25), 25 mg/kg (CIS + CR25), and 100 mg/kg (CIS + CR100). CIS and CIS + CR groups received a single intraperitoneally (i.p.) injection of CIS (7 mg/kg). CR (6.25–100 mg/kg i.p.) injections were started three days before the CIS injection and continued once a day for up to 13 days. On the 14th day, all animals were sacrificed and their blood samples and testes were removed for biochemical and histological analyses.Results: Compared to the control group, CIS significantly decreased relative testis weight (0.28 vs. 0.39,p < 0.001), testosterone level (0.3 vs. 2.31 ng/mL,p < 0.001), germinal layer area (25,886 vs. 35,320 µm²,p < 0.001), superoxide dismutase (SOD) (0.9 vs.1.73 U/mg,p < 0.001) and increased testicular lipid peroxidation (3.05 vs. 15.35 nmol/mg,p < 0.001). CR at 25 mg/kg ameliorated testicular lipid peroxidation and enhanced SOD activity compared to CIS group (p < 0.05). Besides, CR treatment at the maximum dose (100 mg/kg) resulted in reversing CIS effects on testis weight, testosterone level, SOD, lipid peroxidation, and germinal layer area.Conclusions: These findings demonstrated that CR co-treatment could prevent CIS-induced testicular toxicity in rats.

Introduction: Tramadol is a synthetic opioid which is commonly used around the world to relieve moderate to severe pain. One of the serious possible complications of its use is seizures. The present study aims to investigate and summarize the studies related to tramadol and occurrences of seizures after tramadol use and factors influencing these seizures. Methodology: Our systematic review is compliant with PRISMA guidelines. Two researchers systematically searched PubMed/Medline, Web of Sciences, and Scopus. Cohort, case-control, cross-sectional studies, and clinical trials. The risk of bias was assessed using the Newcastle–Ottawa Scale After article quality assessment, a fixed or random model, as appropriate, was used to pool the results in a meta-analysis. Heterogeneity between the studies was assessed with using I-square and Q-test. Forest plots demonstrating the point and pooled estimates were drawn. Results: A total of 51 articles with total sample size of 101 770 patients were included. The results showed that seizure event rate in the subgroups of tramadol poisoning, therapeutic dosage of tramadol, and tramadol abusers was 38% (95% CI: 27–49%), 3% (95% CI: 2–3%), 37% (95% CI: 12–62%), respectively. Tramadol dose was significantly higher in the patients with seizures than those without (mean differences: 0.82, CI 95%: 0.17–1.46). The odds for occurrence of seizures were significantly associated with male gender (pooled OR: 2.24, CI 95%: 1.80–2.77). Naloxone administration was not associated to the occurrence of seizures (pooled OR: 0.47, 95% CI: 0.15–1.49). Conclusions: Our results demonstrate that the occurrence of seizures in patients exposed to tramadol are dose-dependent and related to male gender, but not related to naloxone administration. Given that, most of the evidence derives from studies utilizing a cross-sectional design, the association of tramadol with seizures should not be considered to be definitively established

There is a variety of experimentally proven medicinal plants having antidiabetic properties but data on herb-drug interaction are very limited. Earlier studies indicated that aqueous extract of turnip leaf (AETL) has hypoglycemic potential in diabetic animals. The present study was conducted to evaluate co-administration effects of AETL and metformin, a commonly used antidiabetic drug, in diabetic rats. Metformin at the two different doses (50,100 mg/kg) and AETL at the dose of 400 mg/kg (separately or concurrent with metformin) were orally given to streptozotocin-induced diabetic rats for 4 weeks daily. Fasting blood glucose (FBG) was measured at the times 0, 7, 14, 21 and 28 days after investigation. At the end of study, liver enzymes activity [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] as well as liver histopathology were evaluated. Both treatments could significantly decrease FBG levels when they administrated separately. Interestingly, co-administration of AETL and metformin in a dose dependent manner significantly improved hypoglycemic activity of metformin. While neither metformin nor AETL could ameliorate liver alterations alone, but in concomitant therapy they efficiently attenuated liver enzymes elevation and histological damages. The results of the present study demonstrate that combination of metformin with AETL enhance the prior effectiveness and reduced the latter adverse effects by a synergistic interaction.