Manganese exacerbated chronic khat-induced neurological deficits, inflammation and organ toxicity in a mouse model

Impact of Khat (Catha edulis) Chewing on Inflammatory Markers and Advanced Glycation End Products among Yemeni Women

“…A recent study found that khat extract increased levels of the pro-inflammatory cytokine TNFalpha, IL-6, and WBC (lymphocytes, monocytes, neutrophils, and eosinophil) were elevated in a mouse model [10,11]. In contrast, a previous study reported that secretion of inflammatory cytokines (TNFα and IL-6) was inhibited in khattreated peripheral blood mononuclear cells, whereas khat increased anti-inflammatory cytokine IL-10 and IL-2 [12].…”

Preparatory work for the update of the tolerable upper intake levels for manganese

“…A study where mice were exposed to 720 mg Mn per kg body weight in their drinking water used rapid murine comma and behaviour score to assess neuronal integrity, general well-being and neurological function (Chepukosi et al, 2021) and found reduction in the scores. Gait, motor performance and aggression were part of the score and in this study the authors found that manganese reduced scores of all three parameters.…”

“…Four single dose studies investigated other endpoints, that do not fit under LOE1 to LOE3 or LOE5. Four of these studies used mice (Chepukosi et al, 2021;Krishna et al, 2014;Wilcox et al, 2022) and one used rats (Zhang et al, 2021). The study using male rats, exposed them to 30.5 mg Mn per kg for 3 months and performed a sunflower seed eating test.…”

“…In conclusion, it is difficult to draw conclusions from the few studies with a broad spectrum of outcomes and range of manganese doses used (from 19.0 mg Mn to 720.0 mg Mn). Four studies found an effect of manganese on measured outcomes (Avila et al, 2008;Chepukosi et al, 2021;Krishna et al, 2014;Zhang et al, 2021) at dose range from 30.5 (Avila) to 720 g/kg bw (Chepukosi). Two studies, with dose range between 19 to 720 mg/kg bw, found no effects (Dorman et al, 2000;Wilcox et al, 2022), which is in line with the other lines of evidence above that indications on impaired neurodevelopment are frequently detected in individual studies while at the same time the consistency between the same sensitive tests performed in comparable studies is not always present.…”