Spirulina platensis Ameliorates Oxidative Stress Associated with Antiretroviral Drugs in HepG2 Cells

Abstract

Lately, Spirulina platensis (SP), as an antioxidant, has exhibited high potency in the treatment of oxidative stress, diabetes, immune disorder, inflammatory stress, and bacterial and viral-related diseases. This study investigated the possible protective role of Spirulina platensis against ARV-induced oxidative stress in HepG2 cells. Human liver (HepG2) cells were treated with ARVs ((Lamivudine (3TC): 1.51 µg/mL, tenofovir disoproxil fumarate (TDF): 0.3 µg/mL and Emtricitabine (FTC): 1.8 µg/mL)) for 96 h and thereafter treated with 1.5 µg/mL Spirulina platensis for 24 h. After the treatments, the gene and protein expressions of the antioxidant response pathway were determined using a quantitative polymerase chain reaction (qPCR) and Western blots. The results show that Spirulina platensis decreased the gene expressions of Akt (p < 0.0001) and eNOS (↓p < 0.0001) while, on the contrary, it increased the transcript levels of NRF-2 (↑p = 0.0021), Keap1 (↑p = 0.0002), CAT (↑p < 0.0001), and NQO-1 (↑p = 0.1432) in the HepG2 cells. Furthermore, the results show that Spirulina platensis also decreased the protein expressions of NRF-2 (↓p = 0.1226) and pNRF-2 (↓p = 0.0203). Interestingly, HAART-SP induced an NRF-2 pathway response through upregulating NRF-2 (except for FTC-SP) (↑p < 0.0001), CAT (↑p < 0.0001), and NQO-1 (except for FTC-SP) (↑p < 0.0001) mRNA expression. In addition, NRF-2 (↑p = 0.0085) and pNRF-2 (↑p < 0.0001) protein expression was upregulated in the HepG2 cells post-exposure to HAART-SP. The results, therefore, allude to the fact that Spirulina platensis has the potential to mitigate HAART-adverse drug reactions (HAART toxicity) through the activation of antioxidant response in HepG2 cells. We hereby recommend further studies on Spirulina platensis and HAART synergy.