Effect | Amodiaquine | Amoxicillin | Nevirapine | Clozapine |
---|---|---|---|---|
Organ weight | Multiple organs ↓/—a | Spleen —a | Liver —/↑a | Liver, heart —/↑a |
Liver | ALT ↑a Covalent bindinga | ALT ↑a | ALT ↑a Inflammatory lesionsa Covalent bindinga | ALT ↑a Inflammatory lesionsa Covalent bindinga |
Other organs | Covalent binding: kidney, spleen, guta | Covalent binding: serum albuminb | n.d. | Decreased splenic white pulpa Ovarian, kidney damagea Cardiac inflammation a,b |
Cell death or proliferation | Apoptosis ↑a | Apoptosis ↑a | Apoptosis ↑a Apoptosis ↓b | Apoptosis ↑a Proliferation ↓a AIF translocation –a,b |
Immune cells | Leukocytes ↓ then ↑a NK cells ↑a | Leukocytes ↓/↑a Leukocytes –b | Leukocytes ↓/↑a Leukocytes ↑b | Neutrophils ↑a,b Eosinophils, neutrophils, monocytes ↑b |
Inflammatory mediators | Many cytokines ↑a | n.d. | TNF-α ↑a IFN-γ –a Mixed effect on cytokines ± HIV infectionb | CXCL2, TNF-α ↑a Soluble TNFR, soluble CD8, soluble IL-2R, TNF-α ↑b Arachidonic acid signaling ↔a IL-6 ↑a,b |
Signal transduction | n.d. | n.d. | n.d. | NF-κB ↑/–a AMPK-ULK1-Beclin1↑a PERK/eIF2α ER stress ↑a |
Mitochondria and oxidative stress | n.d. | Cytochrome-c ↑a Malondialdehyde ↑a | Malondialdehyde ↑a Mitochondrial dysfunction ↑a Mitochondrial dysfunction ↑/–b | Malondialdehyde ↑a Mitochondrial dysfunction ↑a |
↑, increase; —, no change; ↓, decrease; AIF, apoptosis-inducing factor; AMPK-ULK1-Beclin1, AMP-activated protein kinase-Unc-51-like kinase 1-Beclin1; IL-2R, IL-2 receptor; n.d., no data; PERK/eIF2α, protein kinase R–like ER kinase/eukaryotic translation initiation factor 2A; TNFR, TNF receptor.
↵a Rodent study
↵b Human study