Noora Kadhim Hadi Alyasari

Background: Doxorubicin-induced cardiotoxicity (DIC) is a major complication of cancer chemotherapy. Thus, developing effective myocardial protection strategies during doxorubicin (Dox) therapy is a medical necessity. Objectives: To evaluate and compare the cardioprotective effectiveness of free berberine (Ber) and berberine loaded in micelles (mBer) against DIC. Materials and Methods: The study, which was conducted in 2023, employed the H9c2 cell line, derived from embryonic cardiomyocytes, as a model. The study included a control group and six experimental groups: the Ber-treated group, the mBer-treated group, the Dox-treated group, the Ber-Dox combination-treated group, and the mBer-Dox combination-treated group, as well as the void micelles-treated group. The study evaluated the alterations in several cardiotoxicity markers with triplicate measurements: [lactate dehydrogenase (LDH), creatine kinase myocardial band (CK-MB), and cardiac troponin I (cTn-1)], lipid peroxidation indicator (malondialdehyde (MDA), oxidative stress markers [Reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD), inflammatory cytokines (interleukin-1β (IL-1β) and interleukin-6 (IL-6)], and the activity of the apoptosis proteins caspases 3/7. Results: The DOX group demonstrated significant increases in cardiotoxicity enzyme indices, lipid peroxidation, generation of free radicals, inflammatory cytokines, and caspase 3/7 activity relative to the control group. When Ber, or mBer, was co-delivered with Dox, the levels of LDH, CK-MB, cTn-1, and MDA significantly decreased. Whereas the activities of SOD and CAT were significantly improved when Ber, or mBer, was co-delivered with Dox. They reduced the elevation in both IL- β and IL-6 levels as well as the activities of caspases 3 and 7 induced by Dox. Importantly, the utilization of the micellar formulation of Ber in conjunction with Dox significantly enhanced the cardioprotective efficacy of Ber against DIC in H9c2 cells. Conclusion: Our results suggest that mBer offers a novel Ber delivery approach and prospective therapeutic strategy for the treatment of DIC.

The objective of this investigation was to find out whether L-carnitine-loaded nanoparticle (LCn) could reduce the reproductive toxicity of cypermethrin (CYP), the widely used insecticide in veterinary medicine in male rats. Twenty male Wistar rats that weighed between 210 and 240 g were split into four groups and treated daily for 2 months. The control group was given 0.9% normal saline solution daily. The second group received CYP (3.83 mg/kg b. w. p. o.) daily. The third group was administered with LCn and CYP (50 mg/kg b. wt. p. o. and 3.83 mg/kg b. wt. p. o., respectively) daily, whereas the fourth group received LCn alone (50 mg/kg b. wt. p. o.) daily. On day 60, all rats were sacrificed and samples were collected. CYP-treated animals exhibited inhibition of testicular anti-oxidative stress mechanisms, testicular steroidogenesis enzyme activity (3β-hydroxysteroid dehydrogenase [3β-HSD] and 17β-HSD), and downregulation of steroidogenic acute regulatory (StAR) gene expression. In addition, it decreased testosterone, follicle-stimulating hormone, and LH levels and had detrimental consequences for sperm quality. LCn attenuated CYP-induced reproductive toxicity via the alleviation of testicular oxidative stress status, improvement of steroidogenic enzyme activity, and upregulation of StAR gene expression, which are probably responsible for the concomitant improvement in testicular hormonal levels and improvement in sperm properties. Intriguingly, LCn treatment alone could enhance the functions of the male reproductive system.