Fluoride and aluminum are ubiquitous toxic metals with adverse reproductive effects. The citrus flavonoid hesperidin has
protective activities but poor solubility and bioavailability. Nanoparticulate delivery systems can improve flavonoid effectiveness.
We conducted this study to prepare a pH-responsive chitosan-based nanogel for hesperidin delivery and evaluate its
effectiveness against sodium fluoride (NaF) and aluminum chloride (
AlCl3) induced testicular toxicity in mice. The nanogel
was synthesized using 2 kGy gamma irradiation, enabling a size under 200 nm and enhanced hesperidin release at pH 6
matching testicular acidity. Male mice received 200 mg/kg AlCl3
and 10 mg/kg NaF daily for 30 days. Hesperidin nanogel
at 20 mg/kg was administered orally either prophylactically (pretreatment) or after intoxication (posttreatment). The results
showed that AlCl3
+ NaF induced severe oxidative stress, hormonal disturbance, apoptosis, and endoplasmic reticulum stress,
evidenced by significant changes in the studied parameters and testicular histological damage. Hesperidin nanogel administration
significantly inhibited oxidative stress markers, restored luteinizing hormone (LH), follicle-stimulating hormone
(FSH), and testosterone levels, and alleviated tissue damage compared to the intoxicated group. It also downregulated the
expression level of pro-apoptotic genes Bax, caspase-3, caspase-9, and P38MAPK, while upregulating the expression level
of the anti-apoptotic BCL2 gene. Endoplasmic reticulum stress sensors PERK, ATF6, and IRE-α were also downregulated
by the nanogel. The chitosan-based nanogel enhanced the delivery and efficacy of poorly bioavailable hesperidin, exhibiting
remarkable protective effects against AlCl3
and NaF reproductive toxicity. This innovative nanosystem represents a
promising approach to harnessing bioactive phytochemicals with delivery challenges, enabling protective effects against
chemical-induced testicular damage |
