Comment for authors
The article ‘amelioration of cyclosporine-induced testicular toxicity by carvedilol and/or alpha-lipoic acid: Role of TGF-β1, the proinflammatory cytokines, Nrf2/HO-1 pathway and apoptosis’ reports the protective role of carvedilol and alpha-lipoic acid alone and combination treatment against the cyclosporine-induced testicular and sperm damage by amelioration of inflammation and oxidative stress. The study experimental design and methods are appropriate, but in the current form of manuscript required some changes and/or corrections. This reviewer has following comments.
1. Why author choose 45 days treatment and experimental model to evaluate the possible beneficial effect of alone and combination therapy. Is there any specific preseason for this? Do they have some pharmacokinetic information for induction of testicular toxicity or protection?
2. Most of methods are written very briefly with as manufacture instructions, better to provide more details or catalogue numbers details, which help peer to fellow the article methods.
3. Table-2: Mentioned unit for the GET and STD.
4. In figure-1 statistics is not clear the significant level provide is at end of study or any time point. Better to determine the statistical significance for all time point. Even better to mention exact significance level with number of asterisk or symbols rather than just mentioning p<0.05.
5. Merage figure 2 and 3 in one figure. Also, arrows in figure 3 arrow are very thin and red color. Change them to other color and visible.
6. Figure 4 axis labels are very small font size, its not readable increased font size of axis label. Also, confirm the unit of TBARS. Is this assay being a kinetic assay or measure activities per minutes for lipid peroxidation?
7. In figure 6, cyclosporin + CMC group testicular damage look more severe than alone cyclosporine. Is there any biological effect of CMC in testes report? Author should provide some explanation for this.
8. There is no information of number sample (n) analyses for different assays. Mentioned exact number or sample size in legends of each figures and tables.
9. All abbreviation for are mentioned in material and methods which is last part of manuscript. Provide abbreviations at its first appearance.