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Pomegranate Seeds Extract Possesses a Protective Effect against Tramadol-Induced Testicular Toxicity in Experimental
Fatma M Minisy1,2, Hossam H Shawki1,3, Abdelfatteh El Omri4
1Department of Comparative and Experimental Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Abstract:
Tramadol is a centrally acting opioid analgesic that is extensively used. The chronic exposure to tramadol induces oxidative stress and toxicity especially for patients consuming it several times a day. Previously, we and others reported that tramadol induces testicular damage in rats. This study was conducted to investigate the possible protective effect of pomegranate seed extract (PgSE) against tramadol-induced testicular damage in adult and adolescent rats. Male rats were orally treated with tramadol or in a combination with PgSE for three weeks. Testes were then dissected and analyzed. Histological and ultrastructural examinations indicated that tramadol induced many structural changes in the testes of adult and adolescent rats including hemorrhage of blood vessels, intercellular spaces, interstitial vacuoles, exfoliation of germ cells in lumen, cell apoptosis, chromatin degeneration of elongated spermatids, and malformation of sperm axonemes. Interestingly, these abnormalities were not observed in tramadol/PgSE cotreated rats. The morphometric analysis revealed that tramadol disrupted collagen metabolism by elevating testicular levels of collagen fibers but that was protected in tramadol/PgSE cotreatment at both ages. In addition, DNA ploidy revealed that S phase of the cell cycle was diminished when adult and adolescent rats were treated with tramadol. However, the S phase had a normal cell population in the cotreated adult rats, but adolescent rats had a lower population than controls. Furthermore, the phytochemistry of PgSE revealed a high content of total polyphenols and total flavonoids within this extract; besides, the DPPH free radical scavenging activity was high. In conclusion, this study indicated that PgSE has a prophylactic effect against tramadol-induced testicular damage in both adult and adolescent ages, although the tramadol toxicity was higher in adolescent age to be completely protected. This prophylactic effect might be due to the high antioxidant compounds within the pomegranate seeds.
Insights
Pomegranate seed extract (PgSE) protects against tramadol-induced testicular damage in adult and adolescent rats. This protective effect is attributed to the antioxidant compounds in pomegranate seeds.
Area of Science:
- Toxicology
- Pharmacology
- Reproductive Biology
Background:
- Chronic tramadol use can cause oxidative stress and toxicity.
- Tramadol has been previously shown to induce testicular damage in rats.
Purpose of the Study:
- To investigate the protective effect of pomegranate seed extract (PgSE) against tramadol-induced testicular damage.
- To compare the effects in adult and adolescent rats.
Main Methods:
- Male rats (adult and adolescent) were treated with tramadol alone or in combination with PgSE for three weeks.
- Testes were analyzed using histological, ultrastructural, morphometric, and DNA ploidy assessments.
- Phytochemical analysis of PgSE and its antioxidant activity (DPPH assay) were performed.
Main Results:
- Tramadol induced significant testicular structural damage, including apoptosis and sperm malformation, in both age groups.
- PgSE co-treatment prevented most tramadol-induced abnormalities and protected collagen metabolism.
- Tramadol reduced S phase of the cell cycle, which was partially restored by PgSE, especially in adults.
Conclusions:
- PgSE exhibits a prophylactic effect against tramadol-induced testicular damage in adult and adolescent rats.
- The high polyphenol and flavonoid content, along with antioxidant activity, likely contributes to PgSE's protective effects.
- Adolescent rats showed higher tramadol toxicity, with less complete protection from PgSE compared to adults.