Hesperidin (Hes) functions as a strong antioxidant and anti-inflammatory to guard against damage to the heart, liver, and kidneys. Nevertheless, due to its restricted solubility and bioavail
ability, a delivery method is required for it to reach a specific organ. In this study, ion gelation was
used to synthesize a chitosan/hesperidin nanoformulation. Numerous characterization techniques,
such as zeta potential, particle size, XRD, TEM, SEM, and FTIR analyses, were used to corroborate
the synthesis of hesperidin nanoparticles (Hes-NPs). Male albino mice were given a pretreatment
dose of 100 mg/kg, PO, of Hes or Hes-NPs, which was administered daily for 14 days before the
induction of doxorubicin nephrotoxicity on the 12th day. Kidney function (urea and creatinine levels)
was measured. Lipid peroxidation (MDA) and antioxidant enzyme (CAT and SOD) activities were
estimated. TNF-α, IL-1β, and VEGF content; histopathological examination of kidney tissue; and
immunohistochemical staining of NF-κB, Caspase-3, BAX, Bcl-2, and TGF-β1 were evaluated. The
gene expressions of Sirt-1, Bcl-2, VEGF, HIF1-α, and Kim-1 were also considered. The results showed
that pretreatment with Hes or Hes-NPs reduced doxorubicin’s nephrotoxic effects, with Hes-NPs
showing the greatest reduction. Kidney enzyme and MDA content were lowered in response to the
Hes or Hes-NP pretreatment, whereas antioxidant enzyme activities were increased. Hes or Hes-NP
pretreatment suppressed the levels of TNF-α, IL-1β, VEGF, NF-κB, Caspase-3, BAX, and TGF-β1;
however, pretreatment increased Bcl-2 protein levels. Furthermore, the gene expressions of Sirt-1,
Bcl-2, VEGF, HIF1-α, and Kim-1 were considerably higher with Hes-NP than with Hes treatment.
These results suggest that Hes-NP treatment might reduce DOX-induced nephrotoxicity in mice via
modulating Sirt-1/HIF1-α/VEGF/NF-κB signaling to provide antioxidant, anti-inflammatory, and
anti-apoptotic effects. |
