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Letter to the Editor re ‘Effects of hypothermia and pentoxifylline on the adnexal torsion/detorsion injuries in a rat testis model’

Dear Editor, With attention and curiosity, we read the article by Elmimehr et al. (Elmimehr et al., 2021). We were especially impressed by the fact that the cooling did not contribute to better values of the observed parameters. As early as 1990, it was shown that the application of an ice bath to the ischaemic testis, after 30 min of normothermic ischaemia, significantly improves the vitality of the germinal epithelium (Miller et al., 1990). It has been unequivocally found that lower temperature favourably affects pH, lactate values and testicular tissue morphology itself. Acidification is reduced, while the increase in lactate concentration is reduced by a decrease in temperature (Kallerhoff et al., 1996). The protective effects of hypothermia, in ischaemic testes, are reflected in histological and tubular changes. Cold rather than warm ischaemia has been shown to be essential for the maintenance of morphologically and functionally normal Sertoli and Leydig cells (Sarica & Bakir, 1999; Young et al., 1988). A better Cosentino score was recorded in the groups, where hypothermia was performed (Haj et al., 2007). Also, oxidative stress indicators, such as MDA, MPO and SOD, are significantly lower in both serum and tissue after hypothermia, while antioxidant indicators such as GPx and CAT are significantly higher (Erdem et al., 2019). In the domain of all research on this topic, the temperature of 4°C proved to be the most optimal. In evaluating the effectiveness of hypothermia as a protective strategy, there are three key variables: the time of onset of hypothermia from the moment of torsion, the duration of controlled hypothermia, and the temperature of hypothermia. When using drugs, it should be borne in mind that hypothermia as a nonphysiological condition alters the usual pharmacokinetics and pharmacodynamics of drugs. The function of cytochrome P450 and other enzymes decreases during hypothermia resulting in reduced clearance and longer elimination halflife. Due to the above facts, it is necessary to check the concentrations and titrate the doses of drugs. The study by Dhulqarnain et al. showed that intraperitoneal administration of a single acute 100 mg/kg pentoxifylline dose restored impaired spermatogenesis caused by 2h, 720° testicular torsion and detorsion by increased histopathological scores, increased diameter of seminiferous tubules and increase in the number of germ cell line, but no significant improvement was observed with chronic administration of pentoxifylline of 25 mg/kg for 2 weeks (Dhulqarnain et al., 2021). In the domain of these data, the wellknown fact that the rate of blood return at the time of detorsion is inversely proportional to the duration of torsion. Thus, the vascular capacity for the delivery of antioxidants at the critical moment is much smaller, and various studies have shown that the first 60– 90 min of detorsion is crucial in reperfusion damage (Prillaman & Turner, 1997). Research has been done on mature rats, but we know that testicular torsion most commonly occurs in neonatal and pubertal age. For such a model, the most suitable models are rats aged 35– 50 days. It is also important to note that it is at puberty that testicular tissue is most susceptible to ischaemiareperfusion injury (Heindel et al., 1990). Although intraperitoneal administration of pentoxifylline is appropriate for this model, it would be desirable to see results after intravenous or oral administration as the pharmacokinetics and pharmacodynamics of pentoxifylline are well investigated (Ward & Clissold, 1987).