Background: Many therapies to treat cancer are gonadotoxic and can lead to infertility. New strategies to diminish the side effects and protective plans during and after chemotherapy are needed. Therefore, bone marrow mesenchymal stem cells (BM-MSCs) as a novel solution were investigated against doxorubicin (Dox)-induced toxicity in rat testes. Methods: Forty male albino prepubertal rats were divided into four groups, 10 rats per each group. The first was injected intraperitoneally with saline as control. The second group was injected intravenously with a single dose of BM-MSCs (2 × 10 6 cells). The third was injected intraperitoneally with a single dose of Dox (5 mg/kg b.wt). The fourth was injected with both Dox and BM-MSCs as previously mentioned. Rats were cohabited each separately with an untreated adult female after 8 weeks of treatment to examine Dox effects on male's fertility. Results: BM-MSCs counteract the deleterious effects of Dox on body, testicular weight as well as sperm quality by increasing sperm concentration and reducing the rate of abnormal sperm. BM-MSCs reduced significantly the testicular oxidative stress by reducing the elevated level of malondialdehyde and increasing the antioxidant capacity. Histologically, the testicular atrophy, severe damage of spermatogenesis and the significant reduction of the diameter and germinative cell layer thickness of the seminiferous tubules caused by Dox were significantly recovered after administration of the BM-MSCs. Conclusion: BM-MSCs have a significant role in restoring the structural efficiency of male reproductive system in rats after Dox treatment.
K E Y W O R D Sbone marrow derived-mesenchymal stem cell, doxorubicin, male fertility, oxidative stress, testicular toxicity
received phosphate-buffered saline (PBS); melatonin group received melatonin (10 mg/kg b.wt./day for 2 months by oral gavage); diabetic untreated group; diabetic group treated with melatonin; diabetic group treated with MSCs (a single intravenous injection of 3 × 10 cell in PBS); and diabetic group co-treated with stem cells and melatonin. The results showed significant improvement in glucose, insulin, total antioxidant, and malondialdehyde level in diabetic rats treated with either MSCs alone or in combination with melatonin. The imumuno-histochemical analysis showed that MSCs and/or melatonin treatment reduced the rate of inflammation and apoptosis of the islet cells as well as increased the rate of pancreatic cell division. Such results were indicated by a significant improvement in the level of TNF-α, IL-10, PCNA, and caspase-3 to levels very close to the control. Co-treatment of MSCs and MT resulted in an improvement in the tissue of the pancreas and reduced number of damaged β-cells. It can be concluded that co-treatment of stem cells and melatonin has a significant role in restoring the structural and functional efficiency of β-cells in the pancreas more than stem cells alone. Such results may be due to the role of melatonin as an antioxidant in increasing the efficiency and vitality of stem cells.
Mefloquine (MQ) is a potent effective antimalarial drug against multiple drug-resistant Plasmodium falciparum. It has been proved that MQ can be given safely during the second and third trimesters. However, there is very limited information on the drug safety during the first trimester. The aim of the present work was to investigate the embryotoxicity and teratogenicity of MQ during critical periods of early development. Wistar rats were orally administered with a single dose of MQ (45 mg/kg bwt or 187 mg/kg bwt) on the 1st, 6th or 13th days of pregnancy. Cyclophosphamide (CPA) was chosen as a positive control. On the 21st day of gestation, standard parameters of reproductive performance and fetal examination were estimated. Malondialdehyde (MDA) level, glutathione reductase activity and glutathione (GSH) content were evaluated in placenta and liver homogenates of mothers and fetuses. The results indicated that MQ did not adversely affect the number of implantation, resorption, litter size and fetal body weight and length. Only groups treated with MQ on the 1st day of gestation exhibited significant decrease in fetal body weight. Examination of fetuses for external, visceral and skeletal changes showed minimal variations involving extension of lateral brain ventricles and renal pelvis and signs of delayed ossification. These variations were accompanied with significant elevation of MDA level and reduction of GSH content of fetal liver. Prenatal exposure to MQ at early pregnancy did not cause any embryolethal or teratogenic effect. It could slightly exacerbate minor variations.
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