Cisplatin-induced human peripheral blood mononuclear cells’ oxidative stress and nephrotoxicity in head and neck cancer patients: the influence of hydrogen peroxide

Abstract

Cisplatin is a widely used antineoplastic agent in the treatment of head and neck cancer. However, it is highly nephrotoxic. Oxidative stress is the main mechanism responsible for cisplatin-induced nephrotoxicity. The aim of this study was to characterize cisplatin-induced nephrotoxicity, oxidative stress in peripheral blood mononuclear cells, and the relationship between them. Twenty-four patients were included in the study. Patients had their blood collected prior to cisplatin administration, and 5 and 20 days after initiating therapy, to assess renal function and to determine oxidative stress with MitoSOX™Red, HDCF-DA, and Amplex Red tests. Renal function was assessed by measuring serum creatinine, creatinine clearance, and blood urea nitrogen (BUN). Serum creatinine and creatinine clearance were used to grade nephrotoxicity using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Compared to baseline values, the mean BUN and serum creatinine increased 135 and 100%, respectively, 5 days after cisplatin infusion. Mean creatinine clearance showed a 43% decrease compared to baseline value. Non-statistically significant changes in superoxide anion (O ), hydrogen peroxide (HO), and general reactive oxygen species production occurred. A higher production of HO was correlated with variation in serum creatinine, and was associated with higher grades for serum creatinine increases and creatinine clearance reductions. Linear regression analyses showed an association between HO production and serum creatinine, creatinine clearance, and BUN levels. These results were observed for 5 days following cisplatin administration. In conclusion, HO production was significantly related to changes in all renal parameters that were evaluated, following the cisplatin infusion.

Natural Product Interventions for Chemotherapy and Radiotherapy-Induced Side Effects

“…In 2016, Shreesh Ojha et al provide a review summarized plant-derived natural products for counteracting cisplatin-induced nephrotoxicity (Ojha et al, 2016 ). Of note, oxidative stress is significantly related to cisplatin-induced nephrotoxicity in head and neck cancer patients (Quintanilha et al, 2018 ). Lycopene has anti-oxidative effect.…”

MiR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity in patients with head and neck cancer

“…The mechanisms of cisplatin-induced nephrotoxicity are not entirely understood. The proposed mechanisms include the following: (1) activation of apoptosis due to cisplatin-induced damage in renal tubular cells [5]; (2) induction of oxidative stress resulting from increased production of reactive oxygen species due to cisplatin-induced damage in mitochondrial DNA [3]; (3) accumulation of cisplatin in renal tubular cells due to the high a nity of cisplatin to the copper transporter CTR1 and the organic cation transporter 2 (OCT2) [6,7]; and (4) inhibition of Na + /K + ATPase pump in renal cells by cisplatin [8].…”

Ginseng extract and its constituents alleviate cisplatin toxicity and reverse cisplatin resistance

“…Oxidative stress is also implicated for cisplatin-induced nephrotoxicity [13]. Following cisplatin administration, it induces the production of H 2 O 2 and 8-OHdG (renal oxidative stress product 8-hydroxy-2′-deoxyguanosine) which is significantly associated with decreased GSH (glutathione) levels, and serum creatinine (SCr) level and creatinine clearance reductions.…”