Shiitake dermatitis: experience of the Poison Control Centre Network in France from 2014 to 2019.

OBJECTIVE: Shiitake mushrooms (Lentinus edodes) are an edible fungus, initially grown in Japan and China that are increasingly marketed in Europe. We previously presented 15 shiitake dermatitis cases reported to Poison Control Centres (PCCs) in France from January 2000 to December 2013. The aim of this study was to describe changes in the number of shiitake dermatitis cases since 2014, and to better describe the clinical characteristics and risk factors of this reaction. CASE SERIES: This observational study is a retrospective review of cases in the French PCCs database between 1 January 2014 and 31 December 2019. Out of 125 shiitake exposures, we identified 59 cases of dermatitis: sex ratio of 1.80 M/F; ages ranging from 19 to 69 years (median: 39 years). Dermatitis occurred after raw or undercooked shiitake consumption (e.g., from the wok, in soup, or on pizza). The rash appeared 1-168 h (median: 48 h) after shiitake ingestion. Linear, erythematous, urticarial papules and plaques developed across the trunk, arms, and legs within a few hours and persisted for 1-40 d (median 10 d). The amount of shiitake eaten (low vs. medium vs. high) significantly increased the duration of dermatitis (median days 4 vs. 7 vs. 15, respectively; p = .007). In all, 38 patients received corticosteroids, antihistamine drugs, or both without demonstrated benefit. All patients made a complete recovery. CONCLUSIONS: The mechanism of shiitake dermatitis is thought to involve lentinan, a heat-labile polysaccharide component. Inadequate cooking clearly seems to be a driver of the occurrence of shiitake dermatitis. This study highlighted a dose-dependent response, suggesting a partial toxic mechanism or a th1-type hypersensitivity mechanism. Treatment is focused on symptom management. Health professionals and the general population should be aware of both the risk associated with inadequately cooked shiitake consumption and the favourable prognosis of this still poorly known toxic dermatitis.

Quality control and immunological activity of lentinan samples produced in China.

Lentinan is widely used as a therapeutic agent for treatment of malignant tumors in clinical practice. The chemical structure of lentinan is highly associated with its biological activity. In this study, the correlation between the structure of lentinan and its immune activity was investigated to assess the function of key parameters that can influence quality control of lentinan. The results showed that the batch-to-batch consistency of two lentinan samples was satisfactory, indicating the stability of production process of lentinan. However, although the chemical composition and triple-helical conformation (THC) of the tested samples were relatively similar, their Mw, polydispersity index (PDI), and Rgz remarkably varied due to different production processes. In vitro immunomodulatory assay reflects that lentinan could stimulate the macrophages phagocytic capacity. Meanwhile, lentinan samples could improve the spleen and thymus indices, promote the proliferation of lymphocytes and adjust for the percentages of CD4+ and CD8+ T cells in vivo. Furthermore, the immunomodulatory effect of lentinan sample B (Mw: 650,700 g/mol) was superior than that of the sample A (Mw: 4,818,700 g/mol). It was noted that the Mw should be detected as a necessary index for quality control of lentinan to ensure stability and effectiveness of the production process.

Structural characterization and antiviral activity of lentinan from Lentinus edodes mycelia against infectious hematopoietic necrosis virus.

A novel lentinan (LNT-I) was extracted from Lentinus edodes mycelia, and purified by an anion-exchange DEAE cellulose column and Sephadex G-200 gel. The structural characterization of LNT-I was determined by gas chromatography-mass spectrometry, high performance gel permeation chromatography, Fourier transform infrared spectrometry and 1D-nuclear magnetic resonance spectroscopy. The results showed that LNT-I was a ß-(1 → 3)-glucan backbone with -(1 → 6)-glucosyl side-branching units terminated by mannosyl and galactosyl residues, and its molecular weight was 3.79 × 105 Da. LNT-I consisted of glucose, mannose and galactose with the molar ratio of 19.26:1.20:1.00. LNT-I represented the prominent antiviral activity to IHNV at MOI of 0.05 and 0.10, respectively. Direct inactivation and the antiviral ability in pre-addition, co-addition and post-addition to IHNV (MOI of 0.05) were 62.34%, 39.60%, 53.63% and 82.38%, respectively under 100 µg/mL of LNT-I. Antiviral mechanisms of LNT-I mainly involved in the direct inactivation and the inhibition of viral replication. Moreover, LNT-I significantly down-regulated the expression level of TNF-α, IL-2 and IL-11, and up-modulated the expression levels of IFN-1 and IFN-γ after challenging with IHNV. The results indicated that the inhibitory effects of LNT-I on IHNV infection were possibly attributed to its regulation of the innate immune responses and specific immunity.

Sulfated lentinan induced mitochondrial dysfunction leads to programmed cell death of tobacco BY-2 cells.

Sulphated lentinan (sLTN) is known to act as a resistance inducer by causing programmed cell death (PCD) in tobacco suspension cells. However, the underlying mechanism of this effect is largely unknown. Using tobacco BY-2 cell model, morphological and biochemical studies revealed that mitochondrial reactive oxygen species (ROS) production and mitochondrial dysfunction contribute to sLNT induced PCD. Cell viability, and HO/PI fluorescence imaging and TUNEL assays confirmed a typical cell death process caused by sLNT. Acetylsalicylic acid (an ROS scavenger), diphenylene iodonium (an inhibitor of NADPH oxidases) and protonophore carbonyl cyanide p-trifluoromethoxyphenyl hydrazone (a protonophore and an uncoupler of mitochondrial oxidative phosphorylation) inhibited sLNT-induced H2O2 generation and cell death, suggesting that ROS generation linked, at least partly, to a mitochondrial dysfunction and caspase-like activation. This conclusion was further confirmed by double-stained cells with the mitochondria-specific marker MitoTracker RedCMXRos and the ROS probe H2DCFDA. Moreover, the sLNT-induced PCD of BY-2 cells required cellular metabolism as up-regulation of the AOX family gene transcripts and induction of the SA biosynthesis, the TCA cycle, and miETC related genes were observed. It is concluded that mitochondria play an essential role in the signaling pathway of sLNT-induced ROS generation, which possibly provided new insight into the sLNT-mediated antiviral response, including PCD.

Lentinan: hematopoietic, immunological, and efficacy studies in a syngeneic model of acute myeloid leukemia.

Lentinan, a beta-glucan nutritional supplement isolated from the shitake mushroom (Lentula edodes), is a biological response modifier with immunostimulatory properties. Concomitantly, the role of beta-glucans as chemoimmunotherapeutic in a number of solid cancers has been widely documented. We investigated the effects of nutritional grade lentinan upon BN rats and in a preclinical syngeneic model of acute myeloid leukemia. BN rats supplemented daily with lentinan exhibited weight gains, increased white blood cells, monocytes, and circulating cytotoxic T-cells; and had a reduction in anti-inflammatory cytokines IL-4, IL-10, and additionally IL-6. Lentinan treatment of BN rats with BNML leukemia resulted in improved cage-side health and reduced cachexia in the terminal stage of this aggressive disease. Combination of lentinan with standards of care in acute myeloid leukemia, idarubicin, and cytarabine increased average survival compared with monotherapy and reduced cachexia. These results indicate that nutritional supplementation of cancer patients with lentinan should be further investigated.

Polysaccharide (ANK-102) from Polianthes tuberosa cells deteriorates the resistance of mice to Listeria monocytogenes infection.

Modulatory effect on the murine self defense system by a newly discovered acidic polysaccharide (ANK-102) produced by P. tuberosa cells in liquid culture was examined. Pretreatment with ANK-102 deteriorated the murine survival against lethal infection of Listeria monocytogenes, an intracellular gram-positive bacterium eliminated mainly by macrophages through T-cell mediated immune response. Pretreatment with ANK-102 resulted in the accumulation of Mac 1 and Mac 2 positive cells in the peritoneal cavity of the infected animals and the reduction of Thy1.2 expression on the surface of the thymocytes. A new type of immunosuppressive polysaccharide ANK-102 was introduced.

The effect of lentinan on fertility and general reproductive performance of the rat.

Lentinan, a polysaccharide [(1 leads to 3)-beta-D-glucan], at 0.01, 0.10 or 1.0 mg/kg/day, was administered i.v. once daily to male rats for 9 weeks and to females for 2 weeks before mating. Some animals continued to be treated until they were killed during gestation: others were killed on day 21 post partum. Selected animals of the F1 generation were retained without further treatment, to provide F2 offspring. Reactions to treatment were generally dose-related and included bruising and cutaneous lesions of the tail and swelling and discolouration of the pinnae. In males given 1.0 mg/kg/day there was a clear evidence of gonadal damage and impairment of reproductive capacity; this effect was less marked at 0.1 mg/kg/day and much reduced at 0.01 mg/kg/day. However, the reproductive performance of the selected F1 pups did not appear to have been affected by the treatment of the F0 parents at any dosage. In animals of both sexes there was a dose-related enlargement of the spleen, with evidence of macrophage infiltration.

The effect of lentinan on pregnancy of the New Zealand white rabbit.

Lentinan at 0.1, 0.3 and 1.0 mg/kg/day was administered i.v. to the New Zealand White rabbit, once daily, on days 6--18 of gestation. There were no significant treatment-related effects of post implantation loss, mean litter size and weight, mean foetal weight or the incidence of minor skeletal or visceral anomalies.

The effect of lentinan on the in utero foetal development of the rat and on postnatal development of the F1 offspring.

Lentinan, a polysaccharide [(1 leads to 3)-beta-D-glucan], at 0.1, 1.0 and 5.0 mg/kg/day was administered i.v. to rats once daily from day 15 of pregnancy to day 21 post partum. All animals were allowed to deliver their young and selected animals of the F1 generation were retained without further treatment, to provide F2 offspring. Reactions to treatment were generally dose-related and included bruising of the tail and swelling and discolouration of the pinnae. Animals at 5.0 mg/kg/day sometimes showed swollen hind limbs and cutaneous lesions of the tail. Mean spleen weight in females was increased at all dosages, more so at 1.0 and 5.0 mg/kg/day. There was no evidence of an adverse effect on litter characteristics, including the pre-weaning development of the F1 offspring, or that treatment of the F0 parents adversely affected post-weaning development and reproductive performance of the F1 offspring.

The effect of lentinan on the in utero embryonic and foetal development of the rat and on postnatal development of the F1 offspring.

Lentinan, a polysaccharide [(1 leads to 3)-beta-D-glucan], at 0.10, 1.0 or 5.0 mg/kg/day was administered i.v. to rats once daily from day 6 until, and including, day 17 of pregnancy. Some animals were killed on day 20 of gestation, others were killed on day 21 post partum. Selected animals of the F1 offspring were retained without further treatment, to provide F2 offspring. Reactions to treatment were generally dose-related and included swelling and discolouration of the pinnae, with occasional cutaneous lesions of the tail and swelling of the hind feet. Spleen weight was increased at all dosages. Litter characteristics at day 20 of pregnancy, including the incidence of abnormality, were not affected by treatment. For dams allowed to litter, mean pup weights were slightly increased, with slight acceleration of some physiological markers before weaning. There was no evidence that treatment of the F0 parents affected the reproductive performance of the F1 offspring.

Chronic intravenous administration of lentinan to the rhesus monkey.

The prolonged effects of overdosage with lentinan in the rhesus monkey are associated with foam cell reactions in lung, liver, kidney, spleen, lymph nodes and bone marrow and with varying degrees of vasculitis and associated reactions. A dose level of 0.5 mg/kg/day was without adverse effect.

The intravenous toxicity of lentinan to the beagle dog.

The i.v administration of lentinan to the Beagle dog induced changes in the cytoplasm of macrophagic cells in the liver, spleen, kidney, lungs, lymph nodes, small intestine. Electron-lucent or filamentous inclusions were demonstrated in the liver, kidney and spleen. A dose level of 0.5 mg/kg/day was without adverse effect.

[Acute toxicity of lentinan in mice and rats (author's transl)].

A new anti-tumor polysaccharide, lentinan (beta-1, 3 Glucan) was studied on the acute toxicities using both sexes of mice (ICR) and rats (CD) treated by intravenously (i.v.) intraperitoneally (i.p.), subcutaneously (s.c.) and orally (p.o). LD50 values in mg/kg body weight were essentially the same regardless of species as well as sexes and estimated as follows: 250-500 (i.v.) greater than 2500 (i.p., s.c., and p.o.). Cyanosis, convulsion and death were observed in both species of animals administered (i.v.) with only higher dosages of lentinan. No remarkable toxic signs being specific from lentinan were observed in any cases of treatment, i.p., s.c., and p.o. Gross findings: enlargement of the spleen (i.v., i.p., s.c.) and coarse nodular surface of the kidney (i.v.) in the both species of animals, erythema of the ears (i.v., i.p., s.c.) in mice, mesenteric petechial hemorrhage of the lung and abdomen (i.v.) enlargement of the mesenteric lymph nodes (i.v.) and edema of the diaphragm and intestine (i.p.) in rats were observed. In parallel, another sample of lentinan for clinical use prepared by freeze-dried procedure was tested in both sexes of mice and rats treated by i.v. alone, comparing with a original sample mentioned above. So far as the acute toxicities of lentinans concerned, no significant differences between two preparations were observed.

[Subacute toxicity study of lentinan in rats. 5-week intravenous treatment (author's transl)].

Male and female JCL : SD rats were treated intravenously with lentinan in 5% mannitol solution at dose levels of 0, 0.03, 3.0 and 30.0 mg/kg/day for 5 weeks. Rats receiving 0.3, 3.0 and 30.0 mg/kg/day showed reddening in ear, tail and scrotum and edema in legs and scrotum after day 3 of treatment. Males receiving 30.0 mg/kg/day gained less body weight than control. Occult blood was found in the urine of rats receiving 30.0 mg/kg/day. With regard to haematology, rats from the treatment groups had low mean values relating to red blood cell count, packed cell volume and haemoglobin, while high white blood cell count were recorded for these rats. Biochemical examinations revealed decreases in albumin level and A/G ratio and increases in beta-globulin and gamma-globulin levels for rats from the treatment groups. Slightly high values of BUN were showed for rats receiving 30.0 mg/kg/day. Organ weight analysis showed dose-dependent increase in the spleen, liver and adrenal. Histopathological changes attributable to treatment included (1) changes in reticuloendothelial system such as proliferation of reticular cells and micronodule of epithelioid cells in the spleen, liver and lymph nodes; (2) arteritis in many organs especially notable in epididymis, intestines and mesentery; (3) haemorrhagic changes in lung, intestines and urinary bladder and secondary changes such as increased chronic nephropathy, hypospermatogenesis, spermatic granuloma in epididymis and granulomatous inflammation in ear, tail and scrotum. The maxim safe dose was estimated to be smaller than 0.03 mg/kg/day for males and 0.03 mg/kg/day for females in the present study.

[Intravenous chronic toxicity of lentinan in rats: 6-month treatment and 3-month recovery (author's transl)].

Chronic toxicity of lentinan was studied in male and female JCL : SD rats. Lentinan was given intravenously into tail vein. Dosage levels employed were 0 (5% mannitol), 0.01, 0.1, 1 (with or without dextran), and 10 mg/kg/day for 6 months in a volume of 1 ml/100 g body weight. After 6 months, the treatment was discontinued and a recovery study was performed for 3 months. Rats receiving 10 mg/kg had redness and necrosis of the tail, the treatment was stopped at week 5, and the rats were sacrificed. Rats receiving 1 mg/kg showed redness of the ear, tail, and scrotum, which was remarkable in the 2nd and 3rd months. Body weight gains were not adversely affected. Laboratory examinations revealed an increase in leukocyte count, decreases in differential eosinophil count and platelet count, and an increase in serum beta-globulin level in drug-treated rats. At autopsy after 6 months, rats from the drug-treated groups had pulmonary hemorrhage and enlargements of the spleen and mesenteric lymph nodes. Histologic changes attributable to treatment included (1) activation of reticulo-endothelial system such as small epithelioid cell nodule in the liver, spleen, and mesenteric lymph nodes, and mobilization of Kupffer cells; (2) arteritis in various organs, especially notable in the spleen, testis, and epididymis ; (3) hemorrhage in the lung; and (4) hypospermatogenesis. All these changes described above had a propensity to recover. The maximum no effect level was estimated to be less than 0.01 mg/kg in the present study in male and female rats.