Zofenopril Calcium

Cyclophosphamide (CYP) is a widely‐used chemotherapeutic drug known to induce ovarian damage and infertility in women. The present study evaluated the potential protective roles of zofenopril, a sulfhydryl‐containing angiotensin‐converting enzyme inhibitor, and thymoquinone (ThQ), alone and in combination, against CYP‐induced ovarian damage in rats. Thirty adult female rats were divided into five groups: a control group that received normal saline; a CYP‐Induced group given a single intraperitoneal (IP) dose of 200 mg/kg CYP on day 17 of the experiment; and three groups pre‐treated with zofenopril, ThQ, or Zofenopril+ThQ for 17 days before CYP‐administration, and continuing for 2 days after CYP exposure. Animals were euthanized, and blood and ovarian tissues were collected 48 h after CYP administration. Serum follicle‐stimulating hormone (FSH), luteinizing hormone (LH), anti‐Müllerian hormone (AMH), and estradiol (E2) levels were measured, as well as the apoptotic biomarker caspase‐3, total antioxidant capacity (TAOC), and tumor necrosis factor (TNF‑α). Ovarian histomorphometry was also assessed. CYP injection induced ovarian injury, characterized by reduced serum AMH and E2 levels, increased FSH and LH levels, oxidative stress, and increased levels of inflammatory and apoptotic markers. In addition, severe ovarian atrophy, regression and degradation of ovarian follicles, and atrophic follicles were observed. Zofenopril and ThQ administration significantly mitigated these CYP‐mediated effects, restoring hormone levels, reducing oxidative stress and inflammation, and improving ovarian histology compared with the CYP‐Induced group. Based on the present study, zofenopril and ThQ have protective effects against CYP‐induced ovarian injury; while co‐administration of zofenopril+ThQ was more effective at inhibiting CYP‐induced effects on TAOC, TNF‑α, and caspase‐3 levels.

As several decades of research have shown the cardioprotective effects of angiotensin-converting enzyme (ACE) inhibitors alone or in combination with diuretics, we were interested in investigating the effects of subchronic therapy of these drugs on ischemia-reperfusion (I/R) damage to the heart, as well as their influence on oxidative status. The research was conducted on 40 spontaneously hypertensive male Wistar Kyoto rats, divided into 4 groups. Animals were treated for four weeks with 10 mg/kg/day zofenopril alone or in combination with hydrochlorothiazide, indapamide and spironolactone per os. After the treatment, hemodynamic measurements, echocardiography and assessment of myocardial function were performed according to Langendorff's retrograde perfusion method. The induced global ischemia model involved 20 min of ischemia followed by 30 min of reperfusion to the heart (I20:R30). Markers of oxidative stress were determined spectrophotometrically from plasma and erythrocyte lysates. Heart and kidney tissue samples were pathohistologically analyzed. Treatment with a combination of ACE inhibitors and diuretics significantly lowered blood pressure in spontaneously hypertensive rats, alleviated left ventricular hypertrophy and increased ejection fraction. On the other hand, treatment with zofenopril and diuretics showed pro-oxidative potential. Pathohistological analysis of heart and kidney tissue samples indicates that subchronic administration of antihypertensive agents does not lead to significant changes in these organs. Since the antihypertensive therapy was relatively short (only 4 weeks), in order to elucidate or deny the prooxidative mechanism, additional studies of a longer time interval are needed and planned.