geranylgeranylacetone and Atrophy

Teprenone (geranylgeranylacetone), an anti-ulcer agent, has been reported to inhibit amyloid-β increase, senile plaque formation, and neuronal degeneration, and improve memory in mouse models of Alzheimer's disease (AD).. We conducted a randomized, double-blind, placebo-controlled study to ascertain teprenone's therapeutic ability for AD.. Patients with mild to moderate AD, with a Mini-Mental State Examination (MMSE) score of 13 to 26, were randomly allocated into two groups depending on the administered drug: donepezil +  placebo (placebo group) and donepezil + teprenone (teprenone group). The primary and secondary endpoints included changes in scores of the Japanese version of the AD Assessment Scale-cognitive subscale (ADAS-J cog) and other evaluations, respectively, including MMSE scores, during a 12-month period after the first administration.. Forty-two and thirty-seven patients were allocated to the teprenone and placebo groups, respectively. ADAS-J cog score changes were not different between groups (placebo, 0.6±0.8; teprenone, 0.4±0.8; p = 0.861). However, MMSE scores significantly improved in the teprenone group (placebo, - 1.2±0.5; teprenone, 0.2±0.5; p = 0.044). Subgroup analysis considering the severity of medial temporal area atrophy revealed that this improvement by teprenone was significant in patients with mild (p = 0.013) but not with severe atrophy (p = 0.611). Adverse events were observed in 17.8 and 10.4% of patients in the placebo and teprenone group, respectively.. Teprenone may be effective for AD when administered before atrophy progression in the medial temporal areas.. UMIN ID: UMIN000016843.

Topics: Aged; Alzheimer Disease; Anti-Ulcer Agents; Atrophy; Cognition; Diterpenes; Donepezil; Double-Blind Method; Drug Monitoring; Drug Repositioning; Female; Humans; Male; Mental Status and Dementia Tests; Nootropic Agents; Severity of Illness Index; Temporal Lobe; Treatment Outcome

Several studies have been reported on the effects of various therapeutic agents in enhancing or suppressing the carcinogenic activity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). However, it is still unknown whether a mucosal protective agent could suppress its carcinogenic activity.. Twenty-five Wistar male rats were divided into four groups: group 1, MNNG alone; group 2, MNNG + tetraprenylacetone; group 3, control; group 4, tetraprenlacetone alone. MNNG 100 mg/mL, was freely given to groups 1 and 2, and tetraprenylacetone (200 mg/kg intraperitoneal) was additionally administered every other day to the rats in groups 2 and 4. The animals were sacrificed at 10 weeks and the gastric mucosa examined.. Atrophic changes were observed in the antrum after 8 weeks of oral administration of MNNG. Furthermore, using immunohistological analysis with 5-bromo-2'-deoxyuridine (BrdU), the proliferative zone was found to be enlarged and shifted upward, although the BrdU labelling index of the proliferative zone was unaltered. Intraperitoneal administration of tetraprenylacetone every other day suppressed the MNNG-induced atrophic change and the alterations proliferative markers. Tetraprenylacetone alone did not have an effect either on morphological or proliferative markers.. These observations suggest that gastric mucosal defensive factors may play critical roles in suppressing atrophic change inducing carcinogenesis by an exogenic carcinogen.

Topics: Animals; Anti-Ulcer Agents; Atrophy; Carcinogens; Diterpenes; Gastric Mucosa; Male; Methylnitronitrosoguanidine; Rats; Rats, Wistar