Table 1.

The toxicity/side effects of CQ and HCQ in human, animal and cell line

Drug	Concentration/dose	Route of administration	Duration	Species/cell line	Toxicity/side effects	Mechanism of toxicity	References
CQ	25, 50, 75,100 and 500 μM	–	12, 24 and 48 h	Schwann cells	Inner glial cells toxicity	Ascorbic acid prevented CQ-induced ROS production and CQ toxicity	[113]
CQ	10–250 μM	–	24 h	ARPE-19 Cells	Retinotoxicity	Activation of autophagy and causing cell death	[114]
CQ	50 mg/kg/day	Oral	4 weeks	Rat	Kidney toxicity	Inhibiting cAMP/PKA/AKT signaling pathway	[115]
CQ	32 mg/kg	Subcutaneously	1 day	Female Mice	Pruritus side effect	Green synthesized ZnO NPs affect the CQ-induced pruritus	[116]
CQ	50 mg/kg/day	Oral	2 months	Rat	Cardio toxicity	Via up-regulation of Rho-kinase1	[117]
CQ	a) 100–300 g b) > 300 g c) Patients who never received chloroquine	Oral	3 months	Human	Macular toxicity	Depends on APO E genotype	[118]
CQ and HCQ	a) CQ: 250–500 mg/day b) HCQ: 200–400 mg/day	Oral	2 months	Human	Ocular toxicity	HCQ has a significantly lower risk of causing ocular toxicity than CQ for its more solubility	[119]

AKT protein kinase B, APO E apolipoprotein E, APE-19 a human retinal pigment epithelial cell line, cAMP cyclic adenosine monophosphate, CQ chloroquine, HCQ hydroxychloroquine, NPs nanoparticles, PKA protein kinase A, ROS reactive oxygen species