**3. Positive effects against mycotoxins**

Due to the increased incidence of contamination with mycotoxins, it has been attempted to use inert feed adsorbents to bind mycotoxins, thus reducing their


**127**

pH 3 [53].

*Zeolites Applications in Veterinary Medicine DOI: http://dx.doi.org/10.5772/intechopen.87969*

phyllosilicates, namely bentonite [32].

**4. Adjuvant in anticancer treatment**

intestinal absorption and toxic effects on animals and animal products. Annually, it is estimated that about 25% of the world's harvested crops are contaminated by mycotoxins, leading to huge agricultural and industrial losses [43]. The first adsorbents successfully used in poultry, swine, sheep and bovine breeding were

The adsorption process is strongly related to the pore size, the adsorbent contact surface, polarity, solubility, and the size of the mycotoxin molecules that are adsorbed (e.g., aflatoxins B1 and B2 have 5.18 Å and aflatoxins G1 and G2 are 6.50 Å). Clinoptilolite has the highest *in vitro* adsorption, over 80% for aflatoxins B1 and G2 [44], with effects demonstrated especially in the poultry industry [45–49], but also in piglets [22], lambs [17] and dairy cattle [50] as are presented in **Table 1**. Studies performed by Serbian researchers have demonstrated *in vivo* and *in vitro* that clinoptilolite preparations adsorb ohratoxin A, zearalenone, aflatoxin B1, B2, G2, T-2 toxin, ergosine, ergocristine, ergocryptine and ergometrine in feed [51, 52]. The proportion of adsorption by clinoptilolite particles of the toxins enumerated *in vitro* varies depending on the concentration of these toxins and can range up to 99%. The main mycotoxins adsorbed by Min-a-Zel Plus, modified clinoptilolite, are: aflatoxin B1–99%, zearalenone—94%, ochratoxin A—96% and ergot alkaloids—97% [51, 52]. In another study, T2 toxin—a secondary metabolite of *Fusarium fungi*—was adsorbed on average in 30% by Min-a-zel Plus, Mycosorb (esterified glucomanane) and mixed binder Mycofix (inorganic binder, bacteria, enzymes and phytogenic material extracted from plants) in *in vitro* conditions at

The first studies of anticancer effect of zeolites were performed at the beginning

of 2001 when it was observed that the treatment with clinoptilolite of different tumors in mice and dogs have improved their life span and tumors have decreased in size [54]. *In vitro* studies using cancer cell cultures revealed the clinoptilolite inhibitory effect on protein kinase B (B-Akt), which reduced the growth of cancer cells and increased their apoptosis. Inhibition occurred only in the presence of serum. This finding suggests that adsorption of serum components may be a possible mode of action. Adsorption of molecules involved in transduction signals, such as inositol, phosphatides and Ca, can contribute to its therapeutic efficacy. It also induces expression of tumor suppressor proteins, p21 WAF1/CIP and p27 KIP1, blocking the growth of cancer cell lines. It is assumed that clinoptilolite reduces the exchange rate of intestinal epithelial cells, prolonging their activity, and that silicates and aluminosilicates can interact directly with some cells by modifying their intracellular pathways, and this leads to the alterations in the regulation of gene expression. Changing the order of interaction of other proteins with membrane proteins may be involved, since membrane transport is required to activate protein kinase B [54]. Studies in mice injected i.v. with melanoma cells but receiving a micronized zeolite through gastric intubation for 28 days, revealed an increase in allogeneic graft versus host (GVH) in lymphocytes in the lymph nodes and a reduction in pulmonary metastases. The researchers' hypothesis is that the local inflammation caused by zeolite application, attracts peritoneal macrophages, and these cells in turn produce TNFα that stimulates spleen T-cells, which amplify the local inflammatory response [55]. Also, a reduction in the metabolic rate of cancer cells and a reduced production of 4-hydroxyinonenal following an anti-cancer treatment (Doxorubicin) along with tribomechanically micronized clinoptilolite, having in

this way a potentiator effect on anticancer drugs, were reported [56].

### **Table 1.**

*The summarized effects of zeolites on mycotoxins as reported in literature data.*

#### *Zeolites Applications in Veterinary Medicine DOI: http://dx.doi.org/10.5772/intechopen.87969*

*Zeolites - New Challenges*

et al. revealed that long-term clinoptilolite administration (from 4 weeks before calving to the next dry period) at different doses (1.25 and 2.5%) did not have adverse effects on the liver and serum glucose concentrations, ketone bodies, total protein and urea did not change, with a higher milk production and a lower ketosis incidence [41]. Moreover, other important minerals such as: Cu, Zn, Fe were not influenced by the long-term administration of clinoptilolite (1.25 and 2.5%), which

Also, in combination with yeast, clinoptilolite (Rumencure: yeast 60% and clinoptilolite 40%) given to cows for a long period (30 days) had no apparent adverse effects on their liver function and on some biochemical parameters (glucose, ketone bodies, blood urea nitrogen and total proteins) [42].

Due to the increased incidence of contamination with mycotoxins, it has been attempted to use inert feed adsorbents to bind mycotoxins, thus reducing their

**Dietary rate Species (N) Effect Ref.**

Decreased the severity of lesions and effectively diminished the detrimental effects of aflatoxins

Zeolite NaA can counteract some of the toxic effects of aflatoxin A in growing broiler chicks

The level of 5% clinoptilolite was better in reduction the effects of alfatoxin than 3% clinoptilolite ratio

Pathohistological examination of liver, bursa of Fabricius and small intestine revealed better protective effects in groups fed with Mycofix-plus than in groups with Minazel Plus and Mycosorb were protective failure was noted

The livers of hens showed very low mycotoxin concentrations

Agonistic effect due to oestrogen reduction

The organozeolite reduced the content of zearalenone in liver, kidneys and muscles Addition of 0.5% Min-a-Zel Plus eliminated zearalenone from all organs, totally

Significantly reduced aflatoxin M1 in milk at an average rate of 56.2%

[45]

[46]

[47]

[48]

[49]

[22]

[17]

[50]

Broiler chickens N = 480

> Male broiler chicks N = 80

Male chicks N = 900

"Ross" broiler chicks N = 160

Laying hens N = 96

Piglets N = 20

Lambs N = 64

Dairy cattle N = 15 farms

*The summarized effects of zeolites on mycotoxins as reported in literature data.*

highlights the safety of this natural compound [19].

**3. Positive effects against mycotoxins**

20 g/kg clinoptilolite in feed contaminated with 1 mg/kg aflatoxins for 42 days

1% synthetic zeolites NaA in feed contaminated with 2.5 mg/kg aflatoxin B1 from 21 to 42 days of age

3 and 5% clinoptilolite in feed contaminated with 2 ppm aflatoxin from day 1 to 7 weeks of age

0.2% Minazel Plus/0.2% Mycosorb/0.2% Mycofix-plus in feed contaminated with 2 ppm T-2

2% clinoptilolite in feed

0.2% Min-a-Zel Plus in feed contaminated with 3 mg/kg zearalenone for 14 days

contaminated with 2.5 ppm aflatoxin

200 g clinoptilolite/animal/day for

toxin for 21 days

B1 for 4 weeks

0.2% organozeolite 0.5% organozeolite in feed contaminated with 8.3 mg ZEN/kg

for 53 days

7 day

**126**

**Table 1.**

intestinal absorption and toxic effects on animals and animal products. Annually, it is estimated that about 25% of the world's harvested crops are contaminated by mycotoxins, leading to huge agricultural and industrial losses [43]. The first adsorbents successfully used in poultry, swine, sheep and bovine breeding were phyllosilicates, namely bentonite [32].

The adsorption process is strongly related to the pore size, the adsorbent contact surface, polarity, solubility, and the size of the mycotoxin molecules that are adsorbed (e.g., aflatoxins B1 and B2 have 5.18 Å and aflatoxins G1 and G2 are 6.50 Å). Clinoptilolite has the highest *in vitro* adsorption, over 80% for aflatoxins B1 and G2 [44], with effects demonstrated especially in the poultry industry [45–49], but also in piglets [22], lambs [17] and dairy cattle [50] as are presented in **Table 1**.

Studies performed by Serbian researchers have demonstrated *in vivo* and *in vitro* that clinoptilolite preparations adsorb ohratoxin A, zearalenone, aflatoxin B1, B2, G2, T-2 toxin, ergosine, ergocristine, ergocryptine and ergometrine in feed [51, 52]. The proportion of adsorption by clinoptilolite particles of the toxins enumerated *in vitro* varies depending on the concentration of these toxins and can range up to 99%. The main mycotoxins adsorbed by Min-a-Zel Plus, modified clinoptilolite, are: aflatoxin B1–99%, zearalenone—94%, ochratoxin A—96% and ergot alkaloids—97% [51, 52]. In another study, T2 toxin—a secondary metabolite of *Fusarium fungi*—was adsorbed on average in 30% by Min-a-zel Plus, Mycosorb (esterified glucomanane) and mixed binder Mycofix (inorganic binder, bacteria, enzymes and phytogenic material extracted from plants) in *in vitro* conditions at pH 3 [53].
