Effects of Amlodipine and its Withdrawal on the Testis of the Adult Albino Rat and the Protective Role of Omega-3 (A Light and an Electron Microscopic Study)

ABSTRACT
Background: The hypertension affects about one third of the adult persons all over the world. Amlodipine is a common drug used for treatment of this disease. Infertility is one of the side effects of amlodipine, but remains not completely explained .
The antioxidant, anti-apoptotic and the anti-inflammatory effects of the omega-3 on many tissues including the testis had been documented.
Aim of the work: To observe the effects of amlodipine exposure on the albino rat testis using a light and an electron microscopy. Also, to assess whether these effects were decreased by withdrawal of the drug or intake of omega-3.
Material and Methods: Forty adult male albino rats were used in this study. They were divided into 4 groups, 10 rats each. Group (1), was the control. Group (2), Amlodipine treated group, the rats received 5 mg of amlodipine besylate dissolved in 333 ml of a normal saline daily orally for 2 months. Group (3), Amlodipine plus omega-3, the rats received 5 mg of amlodipine besylate dissolved in 333 ml of a normal saline daily orally plus omega-3 in a dose of 400 mg/kg b. w. daily orally for 2 months. Group (4), withdrawal group, the rats received 5 mg of amlodipine besylate dissolved in 333 ml of a normal saline daily orally for 2 months, then stop the drug and wait 3 months.
All the animals of group 1, 2 and 3 were sacrificed after 2 months. The rats of group (4) sacrificed after 5 months. The rat testicular functions were assessed histo-pathologically by a light and an electron microscope and biochemically by free serum testosterone level measurement.
Results: Regarding the testosterone level, amlodipine group had significantly lower level than the control and the withdrawal groups. The light microscopical examination of the testicular tissue of group (2) showed marked degenerative changes and arrested spermatogenesis in most seminiferous tubules, while these degenerative changes in group ( 3) appeared milder than that of the previous group. Most of the seminiferous tubules of group (4) retained its normal structure. Electro-microscopic examination of the group of amlodipine revealed several abnormalities such as multiple dilated mitochondria, multiple lipid droplets, and highly cytoplasmic vacuoles. The spermatids of the same group showed inverted acrosome and highly distorted ruptured plasma membrane. The fine structural features of group (3) had minimal vacuolations and lipid droplets. The withdrawal group revealed a nearly normal appearance of the testicular cells.
Conclusion: A low dose of amlodipine causes testicular toxicity but an improvement was occurred after the stoppage of the drug. Also, omega-3 had an ameliorative role on the amlodipine testicular toxicity.