Table 4.
In vivo effect of melatonin in animal models of PD.
| References | Design | Results | Melatonin human equivalent dose for a 75 kg adult |
|---|---|---|---|
| Burton et al. (152) | Wistar rats receiving 6-OHDA injection into the SNc were treated with melatonin (1 and 10 mg/kg, i.p.) | Melatonin treatment inhibited apomorphine-induced rotational behavior | 12 and 120 mg |
| Acuña-Castroviejo et al. (153) | C57BL/6 mice receiving an injection of MPP+ were treated with melatonin (10 mg/kg, i.p.) | Melatonin treatment prevented MPTP-induced lipid peroxidation and TH-positive neuronal loss in striatum | 60 mg |
| Jin et al. (154) | Sprague-Dawley rats receiving an injection of MPP+ into the SNc were treated with melatonin (10 mg/kg, i.p.) | Melatonin treatment reduced lipid peroxidation and protected against DA neuronal loss induced by MPP+ | 120 mg |
| Joo et al. (155) | Sprague-Dawley rats receiving 6-OHDA injections into the striatum were administered with melatonin (3 and 10 mg/kg, i.p.) | Melatonin treatment counteracted the 6-OHDA-induced changes in striatal DA synthesis and levels | 36 and 120 mg |
| Kim et al. (156) | Sprague-Dawley rats receiving 6-OHDA injections into the striatum were treated with melatonin (3 or 10 mg/kg, i.p.) | Melatonin treatment reduced motor deficit and protected against 6-OHDA-induced loss of dopaminergic neurons | 36 and 120 mg |
| Dabbeni-Sala et al. (157) | Sprague-Dawley rats receiving 6-OHDA injection into the SNc were treated with melatonin (50 ± 7.5 μg/h, s.c.) | Melatonin treatment prevented apomorphine-induced rotational behavior and mitochondrial damage | 15 mg |
| Aguiar et al. (158) | Wistar rats receiving 6-OHDA injections into the striatum were administered with melatonin (2, 5, 10, and 25 mg/kg, i.p.) | Melatonin treatment prevented apomorphine-induced rotational behavior and depletion of striatal DA and serotonin levels | 24–300 mg |
| Chen et al. (159) | Wistar rats receiving an injection of MPP+ were treated with melatonin (10 mg/kg, i.p.) | Melatonin decreased MPP+-induced toxicity and recovered GSH levels | 120 mg |
| Khaldy et al. (160) | C57BL/6 mice receiving an injection of MPP+ were treated with melatonin (5 or 10 mg/kg i.p.) | Melatonin protected damage of mitochondrial complex I activity in nigrostriatal neurons | 30 and 60 mg |
| Sharma et al. (161) | Sprague-Dawley rats receiving 6-OHDA injections into the striatum were treated with melatonin (4 μg/mL) in drinking water | Melatonin normalized motor deficits and augmented TH immunoreactivity | 6 mg |
| Singh et al. (162) | Sprague-Dawley rats receiving 6-OHDA injections into the striatum were treated with melatonin (0.5 mg/kg, i.p.) | Melatonin treatment prevented apomorphine-induced rotational behavior | 6 mg |
| Saravanan et al. (163) | Sprague-Dawley rats were injected with rotenone into the SN. Melatonin (10, 20, or 30 mg/kg) was administrated i.p. | Melatonin reduced the levels of hydroxyl radicals in mitochondria and protected GSH levels and antioxidant enzymes activities in SN | 120, 240, and 360 mg |
| Huang et al. (164) | Wistar rats receiving an injection of MPP+ were treated with melatonin (10 mg/kg, i.p.) | Melatonin protected DA neurons from apoptosis induced by MPP+ | 120 mg |
| Tapias et al. (165) | C57BL/6 mice received a single injection of MPTP. Melatonin (20 mg/kg) was given s.c. | Melatonin treatment prevented the MPTP-induced mitochondrial increase of NO, inhibited lipid peroxidation and protected complex I activity in striatum and SNc | 120 mg |
| Patki et al. (166) | C57BL/6 mice received MPTP i.p. injections for 5 weeks. Melatonin (5 mg/kg) was administered i.p. | Melatonin protected against MPTP-induced DA neurons loss and locomotor activity deficit, and recovered mitochondrial respiration, ATP production, and antioxidant enzyme levels in SNc | 30 mg |
| Singhal et al. (167) | Swiss mice treated with maneb plus paraquat received melatonin (30 mg/kg/day, i.p.) | Melatonin treatment protected lipid peroxidation and TH-positive neurons degeneration and prevented apoptosis | 180 mg |
| Gutierrez-Valdez et al. (168) | Wistar rats receiving 6-OHDA injections into the medial forebrain bundle were treated with melatonin (10 mg/kg, p.o.) | Melatonin treatment improved motor performance without causing dyskinesia. Melatonin also protected TH-positive neurons and neuronal ultrastructure of striatum | 120 mg |
| Brito-Armas et al. (169) | Sprague-Dawley rats injected with lentiviral vectors encoding mutant human α-synuclein in the SNc received melatonin treatment (10 mg/kg/day, i.p.) | Melatonin treatment prevented the loss of TH-positive neurons | 120 mg |
| Zaitone et al. (170) | Swiss mice received 4 injections of MPTP. Melatonin was given p.o. (5 or 10 mg/kg/day) | Melatonin treatment recovered motor performance, striatal DA level, GSH, and antioxidant enzyme activities, and reduced lipid peroxidation. Melatonin improved the motor response to L-DOPA | 30 and 60 mg |
| Bassani et al. (171) | Wistar rats were i.p. injected with rotenone. Melatonin (10 mg/kg) was administrated i.p. | Melatonin treatment protect TH-positive neurons in SNc and striatal levels of DA | 120 mg |
| Yildirim et al. (172) | Wistar rats receiving 6-OHDA injections into the medial forebrain bundle were treated with melatonin (10 mg/kg, i.p.) | Melatonin prevented oxidative damage and apoptosis of dopaminergic neurons | 120 mg |
| Naskar et al. (173) | BALB/c mice treated with MPTP received melatonin (10, 20, or 30 mg/kg, i.p.) | Melatonin protected against MPTP-induced TH-positive neurons loss in SNc and enhanced the therapeutic efect of L-DOPA | 60, 120, and 180 mg |
| Ozsoy et al. (174) | Wistar rats receiving 6-OHDA injections into the medial forebrain bundle were treated with melatonin (10 mg/kg/day, i.p.) | Melatonin treatment protected DA neurons against changes in antioxidant enzyme activities and lipid peroxidation | 120 mg |
| Carriere et al. (175) | Sprague Dawley rats were injected with rotenone. Melatonin (4.0 μg/mL) was given in drinking water | Melatonin treatment protected motor deficit and loss of TH-positive neurons in striatum and SNc after rotenone | 6 mg |
| Li et al. (176) | Wistar rats were injected with 6-OHDA in the SNc and ventral tegmental area and received i.p. injections of melatonin (5 mg/kg) | Melatonin prevented DA neuronal damage | 60 mg |
| Lopez et al. (177) | C57BL/6 mice receiving MPTP were administered melatonin (10 mg/kg s.c.) | Melatonin administration prevented the disruption of mitochondrial oxygen consumption, increased NOS activity and reduced locomotor activity induced by MPTP, independently of its anti-inflammatory properties | 60 mg |
| Paul et al. (178) | Wistar rats injected with homocysteine in the SNc received melatonin treatment (10, 20, or 30 mg/kg/day, i.p.) | Treatment of melatonin protected against nigral DA loss and improved mitochondrial complex-I activity in SN | 120, 240, and 360 mg |
The human equivalent dose of melatonin for a 75 kg adult are calculated by normalization of body surface area (54).