Protective effects of caffeic acid phenethyl ester on cadmium-induced testicular injury: A crucial role of antioxidant enzymes in male mice infertility

Abstract

Infertility in men is referred to inability to achieve pregnancy in fertile females after at least one year of regular intercourse. The lack of oxygen in the environment may lead to an imbalance of testes production. Swiss mice were alienated into four groups 10 mice/each. This included one negative normal control group I. The induction of infertility was achieved with injection of cadmium chloride at dose 3 mg/kg body weight for four consecutive days for the rest groups. Group III received vehicle (saline) from the second day of induction for the similar period during the experiment. Infertile mice determined depending on alterations in morphology, motility, and reduced sperm count. Group IV was treated with 3 mg/kg of caffeic acid phenethyl ester (CAPE) per day, for 6 days from the second day of cadmium intoxication. Data showed effectiveness of CAPE significantly through improving the antioxidant enzymes SOD, GST and GSH in testes homogenate and GSH-Px in mice serum that were treated compared to those in the untreated group II (P˂0.001). The histopathology, DNA analysis showed marked improvement in spermatogenesis and DNA intact pattern in treated mice testis. Overall, the results demonstrated the ability of CAPE to improve spermatogenic cells. The data analysis indicated the possibility for the future use of CAPE as an inhibitory agent of infertility. Clinical trials and further studies are required to evaluate the definite medical effects of CAPE based on abundant experimental studies, with predictive future applications in human clinical trials.

Keywords: Antioxidant; Apoptosis; CAPE; Infertility.

Figure 1

Photograph (Top) of testes in normal mice. (Bottom) testes after cadmium intoxication.

Figure 2

Photomicrograph showing double tail sperm from mice of group II (Nigrosin and Eosin x400).

Figure 3

Photomicrograph showing coiled tail sperm group II mice (Nigrosin and Eosin x400).

Figure 4

Agarose gel electrophoreses showing DNA fragmentation in mouse testis induced by cadmium: Lane M DNA molecular weight marker. Lane 1 represents control testis, lane 2 cadmium-intoxicated group II, Lanes 3 represents DNA fragmentation in group III, and lane 4 treated mice with CAPE 3 mg/kg b.wt.

Figure 5

Photomicrograph, showings normal structures of seminiferous tubules and spermatocytes of normal control group I (H&Ex400).

Figure 6

Photomicrograph, showings normal structures of seminiferous tubules and spermatocytes of normal control group I (H&Ex400).

Figure 7

Seminiferous tubule-extensive widening of interstitial spaces (black arrow) in cadmium exposure toxicity (x400).

Figure 8

Seminiferous tubule-extensive widening (black) vacuolations (curved), necrosis (white) in cadmium toxicity (x400).

Figure 9

Seminiferous tubules showings vacuolations, disruption of spermatocyte, edema in cadmium exposure toxicity (x200).

Figure 10

Ghosts of Seminiferous tubule showings extensive necrosis (white), vacuolations (head), in cadmium exposure (x200).

Figure 11

Seminiferous tubules necrosis (black), vacuolations (curved) peri-tubular edema, regenerative changes (white) in CAPE treated group IV (x200).

Figure 12

Seminiferous tubules with regenerative changes (black), edema and interstitial infiltrates in treated CAPE group IV (x400).

Figure 13

The solid lines represent, the linear regression and correlation coefficient (r), P is the significance. (A) There is a moderate positive highly significant correlations between GSH-Px and GSH in tissue (r = 0.729, p < 0.001). (B) There is a strong positive highly significant correlations between GSH-Px and SOD in tissue (r = 0.888, p < 0.001). (C) There is a strong positive highly significant correlations between SOD and GSH in tissue (r = 0.897, p < 0.001).