Inflammatory and oxidative stress in rotavirus infection

Figure 4 Inhibition of rotavirus infection by treatment with antioxidants, nonsteroidal antiinflammatory drugs and peroxisome proliferator-activated receptor gamma agonists. NAC and AA can inhibit the production of ROS, whereas NAC can also affect IκB preventing the cytoplasmic activation of NF-κB. NAC can further inhibit nuclear phosphorylated NF-κB preventing the transcription of pro-inflammatory genes. NSAIDs such as KTP, IND and DCF inhibit Cox-2 leading to a significant inhibition of prostaglandin accumulation. On the other hand, ASA and IBF inhibit activation of NF-κB suppressing the transcription of IFN-α, IFN-β and IFN-γ, cytokines and interleukins. These NSAID treatments significantly inhibit rotavirus infections in cultured cells and mice. PPARγ agonists such as 13(S)-hydroxyoctadecadienoic acid (HODE), ALA and DHA, and thiazolidinediones such as PGZ, RGZ, and 2, 4-thiazolidinedione (TZD) activate PPARγ leading to inhibition of cytoplasmic NF-κB. PPARγ can heterodimerize with the RA-activated RXR for promoting transcription of anti-inflammatory genes. This complex can also cause inhibition of phosphorylated NF-κB which in turn leads to decreased transcription of pro-inflammatory genes. MIT, ER, and PROT are indicated. NAC: N-acetylcysteine; NSAIDs: Nonsteroidal antiinflammatory drugs; PPARγ: Peroxisome proliferator-activated receptor gamma; AA: Ascorbic acid; ROS: Reactive oxygen species; NF-κB: Nuclear factor-κB; KTP: Ketoprofen; IND: Indomethacin; DCF: Diclofenac; Cox-2: Cyclooxygenase-2; ASA: Acetylsalicylic acid; IBF: Ibuprofen; IFN-α: Interferon-α; ALA: Alpha-linolenic acid; DHA: Docosahexaenoic acid; PGZ: Pioglitazone; RGZ: Rosiglitazone; RA: Retinoic acid; RXR: Retinoid X receptor; MIT: Mitochondria; ER: Endoplasmic reticulum; PROT: Proteasome.