Table 2.
Prokinetic effects of exogenous ghrelin on diseased stomach in vivo. GE: gastric emptying; GHRP-6: ghrelin secretagogue receptor 6 (non-synthetic ghrelin receptor agonist); h: hour; iNOS: inducible nitric oxide synthase; IP: intraperitoneal; IV: intravenous; L-NAME: Nω-Nitro-L-arginine-methyl-ester-hydrochloride; NO: nitric oxide; Postop: postoperative; SD: Sprague Dawley.
| Author | Species | Ghrelin type | Effective dose | Methods | Results | Mechanism of action |
|---|---|---|---|---|---|---|
| Trudel L., [29] |
Conscious postop ileus model (SD male rats) | Human ghrelin-28 (IGBMC, France) | 20 μg/kg IV given immediately after meal | Assessment of GE by gastric retention of a phenol red-marked meal | Ghrelin reversed the postop delayed GE | |
|
| ||||||
| Trudel L., [42] | Conscious postop ileus model (female mongrel dogs) | Ghrelin (IGBMC, France) | (i) 100 μg/kg IV on day 2 | Assessment of GE by acetaminophen method | Ghrelin reversed the postop delayed GE | |
| (ii) 4 μg/kg IV on day 3 | ||||||
| (iii) 20 μg/kg IV on day 4given after meal | ||||||
|
| ||||||
| De Winter B., [33] | Conscious LPS septic ileus model (Swiss OFI mice) | (i) Rat ghrelin (Tocris, UK) | (i) Ghrelin: 100 μg/kg | Assessment of GE by the gastric retention of an Evans blue-marked meal | Ghrelin and GHRP-6 accelerated GE in LPS septic ileus mice | |
| (ii) GHRP-6 (Bachem, UK) | (ii) GHRP-6: 20 and100 μg/kg given IP 1h prior to meal | |||||
|
| ||||||
| Poitras P., [31] | Conscious postop ileus ± morphine-treated rat model (male SD rats) | Ghrelin receptor agonist RC-1139 (Rejuvenon Corp., USA) | 2.5–10 mg /Kg IV given immediately after meal | Assessment of GE by the retention of 99mTc-labelled meal | (i) RC-1139 accelerated GE dose-dependently in postop ileus rats | |
| (ii) RC-1139 at 10 mg/Kg accelerated GE in postop ileus + morphine-treated rats | ||||||
|
| ||||||
| Liu Y., [43] |
Conscious Cisplatin-treated adult male C57/6J black mice | Rat ghrelin (Bachem Ltd, UK) | 1 mg/Kg, IP b.i.d | Assessment of gastric emptying by the wet weight of gastric content | Ghrelin improved GE | |
|
| ||||||
| Sallam H., [44] |
Conscious scald-burned model (SD male rats) | Ghrelin (Tocris, USA) | 2 nmol/rat given IP 20 min before meal | Assessment of GE by gastric retention of a phenol red-marked meal | Ghrelin accelerated GE; an effect blocked by pretreatment with atropine | Ghrelin's effects on gastric motility involve the cholinergic pathway |
|
| ||||||
| Venkova K., [45] |
Conscious postop ileus ± morphine-treated rat model (male SD rats) | Ghrelin receptor agonist TZP-101 (Tranzyme Pharma Canada) | 0.1–1 mg /Kg (1ml) IV given 1-2 min before meal | Assessment of GE by the retention of 99mTc-labelled meal | TZP-101 accelerated GE dose-dependently in postop ileus rats ± morphine | |
|
| ||||||
| Qui et al. [40] |
Diabetic mouse model (IP-alloxan-treated C57 mice) | Rat ghrelin GHRP-6(Tocris, UK) |
50–200 μg/Kg given IP prior to meal | Assessment of GE by gastric retention of a phenol red-marked meal | Ghrelin and GHRP-6 at all doses accelerated GE; an effect blocked by atropine or L-NAME. | The effects of Ghrelin and GHRP-6 on GE in diabetic gastroparesis is mediated via the cholinergic pathways |
|
| ||||||
| Qui et al. [41] |
Diabetic guinea pig model (IP-STZ-treated) | Ghrelin GHRP-6 |
20, 50 and 100 μg/Kg given IP prior to meal | Assessment of GE by gastric retention of a phenol red-marked meal | Ghrelin and GHRP-6 at all doses accelerated GE; an effect blocked by atropine. | The effects of Ghrelin and GHRP-6 on GE in diabetic gastroparesis are mediated via the cholinergic pathways |
|
| ||||||
|
Chen Y., [46] |
LPS endotoxemia mouse model (male ICR mice) | Rat ghrelin (Global Peptide Services, UDA) | 20 μg/Kg IP given 15 min before meal | (i) Assessment of GE by gastric retention of a phenol red-marked meal | (i) Ghrelin had no effect on GE | Ghrelin's effect on LPS-delayed GE are mediated via the down regulation of NO |
| (ii) Assessment of plasma NO production by fluorometry | (ii) Ghrelin normalized endotoxemia-induced delayed GE | |||||
| (iii) Assessment of iNos expression by immunohistochemistry | (iii) Ghrelin 20 μg/Kg reduced plasma NO and iNOS expression in the submucosa and musculosa of the stomach | |||||
|
| ||||||
| Zheng Q., [47] |
Diabetic mouse model (IP-alloxan-treated C57 mice) | GHRP-6 (Tocris, UK) | 200 μg/kg given IP prior to meal | Assessment of GE by gastric retention of a phenol red-marked meal | GHRP-6 accelerated diabetic-induced delayed GE; an effect blocked by pretreatment with atropine | GHRP-6 effects on gastric motility involve the cholinergic pathway |