Hi!
I hope I'm in the right place, and I apologise if I've chosen this sub-forum incorrectly. I've read the rules of this sub-forum, but am slightly worried that I've misunderstood them. So if I have miscorrectly chosen this forum please let me know, and I'll delete this thread/move it to the correct one.
Basically I have found this article on NCBI (apologies if the article isn't peer-reviewed - I'm not sure how to tell if an article is peer-reviewed or not) about hepatoxicity of Kratom, Kava, and Khat:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849036/
I'm only interested in the Kratom for now.
It states the following:
I don't really understand enough of what they're saying to be able to process the information given.
Is it correct that they're saying that they aren't sure whether the results can be translated to humans?
I'm confused since they tested "the cytotoxicity on human cell lines". I'm guessing this isn't significant enough to "extrapolate" the data/effects onto actual living humans? (Please excuse my english here. It's not my first language).
So to sum this up, basically I'm asking how toxic Kratom/mitragynine or other alkaloids found in Kratom are to humans.
Any input would be greatly appreciated.
Kind regards!
Mude
I hope I'm in the right place, and I apologise if I've chosen this sub-forum incorrectly. I've read the rules of this sub-forum, but am slightly worried that I've misunderstood them. So if I have miscorrectly chosen this forum please let me know, and I'll delete this thread/move it to the correct one.
Basically I have found this article on NCBI (apologies if the article isn't peer-reviewed - I'm not sure how to tell if an article is peer-reviewed or not) about hepatoxicity of Kratom, Kava, and Khat:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849036/
I'm only interested in the Kratom for now.
It states the following:
"To date, there is scarce information about the toxicity of M. speciosa alkaloid extracts and little is known about the adverse effects that have really originated from mitragynine intake.
The M. speciosa cytotoxicity has been evaluated by three authors in different cell lines [162], brine shrimp [163] and gene mutation assays [164]. Saidin [162] tested the cytotoxicity both of the methanol-chloroform extract (MSE) and of mitragynine (MIT), on human cell lines (HepG2, HEK 293, MCL-5, cHol, and SH-SY5Y).
The MSE inhibited cell proliferation in all cell lines, depending on the dose administered, inducing cell death at 1000 μg/mL and MIT showed a similar model of action.
Even if the activated pathways that led to cell death were different (MSE cell death seemed not to be associated with p53 and caspases pathway, contrary to that caused by MIT), the results of these studies suggest that both the methanol?chloroform extract and its dominant alkaloid mitragynine, generate cytotoxicity effects at doses higher than 100 μg/mL.
In a brine shrimp lethality test, Moklas et al. [163], evaluated the toxicity level of three different preparations of mitragynine: the authors found that the LC50 for the aqueous extract was 98 μL/mL, the crude alkaloid extract exhibited a LC50 value of 62 μL/mL, while mitragynine showed the high toxicity with LC50 of 44 μL/mL.
The potential of mutagenic and antimutagenic activity of M. speciosa was evaluated by Ghazali et al.[164], incubating the aqueous extract of the plant with Salmonella typhimurium TA 98 and TA 100 bacterial strains, in presence and absence of the metabolic activator S9 system.
The Ames test (Salmonella/microsome mutagenicity assay) showed no mutagenic activities for M. speciosa both in presence and in absence of the metabolic activator, and with both bacterial strains, but, in the same experimental conditions, M. speciosa had a strong antimutagenic property.
Several studies were carried out in animal models to evaluate the toxicity of the mitragynine, Macko et al. [165] in 1972, tested, for the first time, mitragynine toxicity in rats and dogs:
he found no adverse effects in rats up to a dose of 40 mg/kg/day six days per week, until the twenty-second day of treatment, when hematological alterations were observed, on the other hand, no toxicity signs were noticed in a group of dogs treated with an oral dose of 5 mg/kg/day of mitragynine for three weeks [52].
Recently, Sabetghadam et al. [53] investigated the sub-chronic exposure to mitragynine of male and female rats, administering oral doses of 1, 10, or 100 mg/kg for 28 days. At the lower doses, there was no evidence of toxic effects (such as tremors or seizures), whereas at a dose of 100 mg/kg, alterations in food intake emerged, with a consequent strong decrease in weight especially in female rats. No deaths occurred at the maximum dosage.
Hematological, biochemical analysis and histopathological examination of the brain, kidneys and liver were performed. With regard to the hematological findings, the authors observed a severe anemia, characterized by a decrease in the red and white blood cells, a reduction of the hematocrit levels with a lowering of the hemoglobin content.
Signs of tissue toxicity were observed in the histopathological analysis performed on the brain, kidney and liver. Local vacuolation and the presence of degenerated necrotic neurons were noticed in the brain; in the kidneys an early state of nephrotoxicity was observed. These findings were highlighted in all the animals exposed to the maximum dosage of mitragynine, in particular in female rats.
The alteration of some biochemical parameters corresponded to the structural modifications discovered in the liver. Very high levels of serum lactate dehydrogenase, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and urea, indices of hepatocellular damage, were observed; there was also an increase in liver weight of all the animals exposed to the maximum dose of mitragynine. The histological liver examination showed moderate destruction of polygonal lobules, dilation of sinusoids and hemorrhagic hepatocytes; there were no signs of centrilobular necrosis or inflammatory cell infiltration.
An increase in triglycerides, cholesterol, AST and ALT values, albumin (indices of hepatic impairment), and the presence of histological evidence for hepatic cellular damages, were also observed by Harizal et al. [45] after acute oral administration of 1000 mg/kg of methanolic extract of M. speciosa in rats. In all the rats of the treated group, the histological analysis revealed a severe hepatotoxicity, with a major number of Kupffer cells, hemorrhagic hepatocytes, sinusoids congestion, steatosis and centrilobular necrosis. These studies show that the sub-chronic dosages (1?10 mg/kg) of mitragynine in rats, which in humans corresponds to a dose of 0.1 to 1.7 mg/kg, seems to be quite safe when compared to those consumed by kratom users: in fact, the content of kratom juice regularly consumed in the northern regions of the Malaysia Peninsular, is equal to approximately 0.3 to 5.1 mg/kg per day and users do not show any side effects related to the chronic use of this substance, as reported by Vicknasingam et al. [41,52].
As mitragynine has proved to be extremely toxic in rats, when administered for a prolonged period at 100 mg/kg, in the future more studies must be carried out on the chronic exposure to mitragynine in more complex living systems with dosages relevant for humans, in order to ascertain the possible link between this substance and the severe hepatotoxicity observed in some of the researches here reported."
The M. speciosa cytotoxicity has been evaluated by three authors in different cell lines [162], brine shrimp [163] and gene mutation assays [164]. Saidin [162] tested the cytotoxicity both of the methanol-chloroform extract (MSE) and of mitragynine (MIT), on human cell lines (HepG2, HEK 293, MCL-5, cHol, and SH-SY5Y).
The MSE inhibited cell proliferation in all cell lines, depending on the dose administered, inducing cell death at 1000 μg/mL and MIT showed a similar model of action.
Even if the activated pathways that led to cell death were different (MSE cell death seemed not to be associated with p53 and caspases pathway, contrary to that caused by MIT), the results of these studies suggest that both the methanol?chloroform extract and its dominant alkaloid mitragynine, generate cytotoxicity effects at doses higher than 100 μg/mL.
In a brine shrimp lethality test, Moklas et al. [163], evaluated the toxicity level of three different preparations of mitragynine: the authors found that the LC50 for the aqueous extract was 98 μL/mL, the crude alkaloid extract exhibited a LC50 value of 62 μL/mL, while mitragynine showed the high toxicity with LC50 of 44 μL/mL.
The potential of mutagenic and antimutagenic activity of M. speciosa was evaluated by Ghazali et al.[164], incubating the aqueous extract of the plant with Salmonella typhimurium TA 98 and TA 100 bacterial strains, in presence and absence of the metabolic activator S9 system.
The Ames test (Salmonella/microsome mutagenicity assay) showed no mutagenic activities for M. speciosa both in presence and in absence of the metabolic activator, and with both bacterial strains, but, in the same experimental conditions, M. speciosa had a strong antimutagenic property.
Several studies were carried out in animal models to evaluate the toxicity of the mitragynine, Macko et al. [165] in 1972, tested, for the first time, mitragynine toxicity in rats and dogs:
he found no adverse effects in rats up to a dose of 40 mg/kg/day six days per week, until the twenty-second day of treatment, when hematological alterations were observed, on the other hand, no toxicity signs were noticed in a group of dogs treated with an oral dose of 5 mg/kg/day of mitragynine for three weeks [52].
Recently, Sabetghadam et al. [53] investigated the sub-chronic exposure to mitragynine of male and female rats, administering oral doses of 1, 10, or 100 mg/kg for 28 days. At the lower doses, there was no evidence of toxic effects (such as tremors or seizures), whereas at a dose of 100 mg/kg, alterations in food intake emerged, with a consequent strong decrease in weight especially in female rats. No deaths occurred at the maximum dosage.
Hematological, biochemical analysis and histopathological examination of the brain, kidneys and liver were performed. With regard to the hematological findings, the authors observed a severe anemia, characterized by a decrease in the red and white blood cells, a reduction of the hematocrit levels with a lowering of the hemoglobin content.
Signs of tissue toxicity were observed in the histopathological analysis performed on the brain, kidney and liver. Local vacuolation and the presence of degenerated necrotic neurons were noticed in the brain; in the kidneys an early state of nephrotoxicity was observed. These findings were highlighted in all the animals exposed to the maximum dosage of mitragynine, in particular in female rats.
The alteration of some biochemical parameters corresponded to the structural modifications discovered in the liver. Very high levels of serum lactate dehydrogenase, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and urea, indices of hepatocellular damage, were observed; there was also an increase in liver weight of all the animals exposed to the maximum dose of mitragynine. The histological liver examination showed moderate destruction of polygonal lobules, dilation of sinusoids and hemorrhagic hepatocytes; there were no signs of centrilobular necrosis or inflammatory cell infiltration.
An increase in triglycerides, cholesterol, AST and ALT values, albumin (indices of hepatic impairment), and the presence of histological evidence for hepatic cellular damages, were also observed by Harizal et al. [45] after acute oral administration of 1000 mg/kg of methanolic extract of M. speciosa in rats. In all the rats of the treated group, the histological analysis revealed a severe hepatotoxicity, with a major number of Kupffer cells, hemorrhagic hepatocytes, sinusoids congestion, steatosis and centrilobular necrosis. These studies show that the sub-chronic dosages (1?10 mg/kg) of mitragynine in rats, which in humans corresponds to a dose of 0.1 to 1.7 mg/kg, seems to be quite safe when compared to those consumed by kratom users: in fact, the content of kratom juice regularly consumed in the northern regions of the Malaysia Peninsular, is equal to approximately 0.3 to 5.1 mg/kg per day and users do not show any side effects related to the chronic use of this substance, as reported by Vicknasingam et al. [41,52].
As mitragynine has proved to be extremely toxic in rats, when administered for a prolonged period at 100 mg/kg, in the future more studies must be carried out on the chronic exposure to mitragynine in more complex living systems with dosages relevant for humans, in order to ascertain the possible link between this substance and the severe hepatotoxicity observed in some of the researches here reported."
I don't really understand enough of what they're saying to be able to process the information given.
Is it correct that they're saying that they aren't sure whether the results can be translated to humans?
I'm confused since they tested "the cytotoxicity on human cell lines". I'm guessing this isn't significant enough to "extrapolate" the data/effects onto actual living humans? (Please excuse my english here. It's not my first language).
So to sum this up, basically I'm asking how toxic Kratom/mitragynine or other alkaloids found in Kratom are to humans.
Any input would be greatly appreciated.
Kind regards!
Mude