Riboflavin Arrests Cisplatin-Induced Neurotoxicity by Ameliorating Cellular Damage in Dorsal Root Ganglion Cells

Abstract

Cis-Diamminedichloroplatinum II- (CP-) induced neurotoxicity is one of the least explored aspects of this drug. Dorsal root ganglia (DRG) cells are considered as the primary target, and their damage plays a vital role in pathogenesis and etiology of CP-induced neurotoxicity. The present study is aimed at confirming if riboflavin (RF) has any protective role in shielding the DRG from CP-induced toxicity. After conducting the established treatment strategy on mice under photoillumination, it was observed that, despite the fact that RF alone is partially toxic, its combination with CP significantly ameliorated the drug-induced damage in DRG cells as evidenced by histological analysis. In addition, it was interesting to observe that the combination group (RF + CP) was able to induce apoptosis in the target cells up to a significant extent which is considered as the most preferred way of countering cancer cells. Therefore, RF can act as an effective adjuvant compound in CP-based chemoradiotherapy to improve clinical outcomes in the contemporary anticancer treatment regimes.

Figure 1

Sample photomicrographs from the thoracic dorsal root ganglia of mice. Control group (a) shows pseudounipolar neuron with centrally placed nucleus and prominent nucleolus (↑) while cisplatin treated group (b) shows relatively small shrunken neuron, smaller nucleolus, and rarified bundle of nerve fibers (N) and prominent neuroglial cells. Riboflavin treated (c) and combination treated (d) groups show neuronal sizes and nucleolar features comparable to control group. All tissue sections were prepared with H&E stain followed by snapping at magnification of 400x. Arrows indicate neurons while stars indicate the nerve fibres.

Figure 2

Showing bar graph of cells undergoing necrosis and apoptosis after the treatment with riboflavin, cisplatin, and their combination in dorsal root ganglia of mice. ∗ indicates significant difference from group I (control) at p ≤ 0.05. # indicates significant difference from group III at p ≤ 0.05.